Protein Tyrosine Kinase

Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

281 | Feb 15 2024

The comprehensive analysis of protein and phosphorylation signatures in cholangiocarcinoma revealed the PRKD family's pivotal role, highlighting their potential as novel treatment targets validated by the inhibitory effects of 1-naphthyl PP1 on CCA cell proliferation, migration, and invasion. [Read the Full Post]

A portable photoacoustic device for facile and sensitive detection of serum alkaline phosphatase activity

66 | Feb 07 2024

The development of a portable photoacoustic device utilizing silver nanoparticles as a signal probe for alkaline phosphatase detection in serum, exhibiting excellent sensitivity, reproducibility, and practical application potential, marks a significant stride in bioassay innovation. [Read the Full Post]

Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system

179 | Jan 29 2024

The identification of significant safety signals for interstitial lung disease associated with several FDA-approved antibody-drug conjugates underscores the critical need for heightened clinician awareness and early patient monitoring, prompting further research and potential adjustments in clinical practice guidelines. [Read the Full Post]

Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial

155 | Jan 29 2024

In HER2-positive breast cancer patients undergoing neoadjuvant dual HER2-targeted therapy, achieving a pathologic complete response or residual cancer burden I in the breast strongly correlates with a high probability of having no residual disease in the axillary lymph nodes, suggesting a potential consideration for omitting axillary surgical staging in future trials for those demonstrating these favorable responses. [Read the Full Post]

Binding Thermodynamics of Fourth-Generation EGFR Inhibitors Revealed by Absolute Binding Free Energy Calculations

100 | Jan 26 2024

Your detailed study on BLU-945 and its analogues' enhanced binding affinities to EGFR mutants sheds critical light on potential mechanisms for combating drug resistance in NSCLC, potentially steering future drug development toward more effective treatments. [Read the Full Post]

Absorption, Metabolism, and Excretion of [14C]-Tolebrutinib After Oral Administration in Humans, Contribution of the Metabolites to Pharmacological Activity

59 | Jan 23 2024

The study on tolebrutinib revealed extensive metabolism generating multiple metabolites, among which metabolite M2, constituting 4% of circulating radioactivity, retained potent inhibition of Bruton's tyrosine kinase akin to the parent compound, suggesting its likely contribution to the drug's pharmacological activity in vivo. [Read the Full Post]

Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01)

82 | Jan 23 2024

The updated analysis of the DESTINY-Breast01 trial underscores the sustained efficacy and generally consistent safety profile of trastuzumab deruxtecan in heavily pretreated patients with HER2-positive metastatic breast cancer, revealing a 62.0% objective response rate, a median overall survival of 29.1 months, and notable treatment-emergent adverse events such as drug-related interstitial lung disease/pneumonitis in 15.8% of patients. [Read the Full Post]

Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

152 | Jan 21 2024

Astragalus polysaccharide alleviates insulin resistance in HepG2 cells by activating the STAT5/IGF-1 pathway, as evidenced by its restoration of impaired glucose uptake and modulation of IGF-1, IGF-1 receptor, AKT, and STAT5 signaling, findings reinforced by the counteraction of its effects by the STAT5 inhibitor AG490. [Read the Full Post]

Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway

77 | Jan 20 2024

The study demonstrates that bone marrow mesenchymal stem cell-derived exosomes loaded with si-PYCR1 suppress aerobic glycolysis and bladder cancer growth via the PI3K/AKT pathway by targeting EGFR, showcasing a promising therapeutic avenue for the disease. [Read the Full Post]

Preclinical Characterization of XL092, a Novel Receptor Tyrosine Kinase Inhibitor of MET, VEGFR2, AXL, and MER

112 | Jan 15 2024

XL092, a multi-receptor tyrosine kinase inhibitor, exhibits potent antitumor effects and immunomodulatory properties in preclinical models, supporting its potential for clinical evaluation, particularly in combination with immune checkpoint inhibitors. [Read the Full Post]

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

218 | Jan 14 2024

PP121, a dual tyrosine and phosphoinositide kinase inhibitor, demonstrates promising anti-contractile and anti-inflammatory effects in asthma treatment, suggesting its potential as a novel therapeutic compound for managing the condition. [Read the Full Post]

Simultaneous inhibition of discoidin domain receptor 1 and integrin αVβ3 radiosensitizes human glioblastoma cells

51 | Jan 14 2024

This study highlights that the combined inhibition of DDR1, integrin αVβ3, and integrin αVβ5 effectively diminishes radioresistance in human glioblastoma cells by disrupting clonogenicity, enhancing cellular radiosensitivity, and impeding DNA repair mechanisms. [Read the Full Post]

Targeting exon 20 insertion mutations in lung cancer

88 | Jan 14 2024

Recent clinical evidence suggests that targeted therapies like mobocertinib and amivantamab offer promising antitumor activity for patients with EGFR exon 20 insertions in non-small cell lung cancer, while ongoing trials with novel treatments such as DZD9008 and CLN-081 hold potential for further improving survival outcomes in this challenging subset of patients. [Read the Full Post]

Polypharmacologic Reprogramming of Tumor-Associated Macrophages toward an Inflammatory Phenotype

101 | Jan 11 2024

This study's establishment of a physiologically relevant in vitro system for TAM polarization unveils BMS-794833 as a potent inhibitor, independent of primary targets but reliant on multiple signaling pathways, offering a promising strategy to reprogram TAMs and suppress cancer growth. [Read the Full Post]

MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer

125 | Jan 10 2024

MTX-211 demonstrates promising potential as a therapeutic agent for bladder cancer by inhibiting cell proliferation through the Keap1/NRF2/GCLM signaling pathway and depleting intracellular GSH levels. [Read the Full Post]

Targeting the survival kinase DYRK1B: A novel approach to overcome radiotherapy-related treatment resistance

64 | Jan 09 2024

Targeting the stress-enhanced survival kinase DYRK1B alongside irradiation demonstrates a synergistic effect in eliminating colorectal tumor cells under harsh environmental stressors, offering a promising strategy to overcome treatment resistance. [Read the Full Post]

HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation

70 | Jan 09 2024

The study unveils a novel relationship where HMGA1 upregulates FGF19, driving pancreatic cancer progression and stroma formation, establishing FGF19 as a potential therapeutic target for a distinct, highly aggressive subset of PDAC. [Read the Full Post]

Active natural compounds perturb the melanoma risk-gene network

179 | Jan 07 2024

The study ingeniously employs network modeling of melanoma-associated genes, revealing crucial pathways and potential therapeutic targets while showcasing the predictive potential of this model in evaluating the efficacy of anti-melanoma phytochemicals. [Read the Full Post]

A pilot study of orelabrutinib treatment in three cases of refractory/relapsed autoimmune haemolytic anaemia/Evans syndrome

85 | Jan 07 2024

The promising response of nine out of twelve patients in our orelabrutinib trial for refractory/relapsed AIHA/Evans Syndrome indicates its potential as a new second-line treatment, offering hope for improved management and quality of life in these conditions. [Read the Full Post]

Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

234 | Jan 06 2024

Sertad1, upregulated in ischemic conditions, exacerbates neurological injury by activating the CDK4/p-Rb pathway, promoting cell cycle dysregulation and apoptotic cell death. [Read the Full Post]

Sulfatinib, a novel multi-targeted tyrosine kinase inhibitor of FGFR1, CSF1R, and VEGFR1-3, suppresses osteosarcoma proliferation and invasion via dual role in tumor cells and tumor microenvironment

109 | Jan 05 2024

Sulfatinib demonstrates promise in inhibiting osteosarcoma growth while altering the tumor microenvironment towards an immune-activated state, offering potential for clinical translation. [Read the Full Post]

FGF2 positively regulates osteoclastogenesis via activating the ERK-CREB pathway

0 | Jan 01 2024

FGF2 influences bone homeostasis by stimulating osteoclastogenesis via the ERK-CREB pathway, suggesting potential therapeutic avenues for bone-related disorders like osteoporosis through targeted inhibition of this signaling cascade. [Read the Full Post]

Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer

114 | Dec 27 2023

The identification of c-Met phosphorylation as a pivotal mechanism driving radioresistance-associated aggressiveness in HNSCC cells offers a promising therapeutic strategy by targeting this pathway with inhibitors like SU11274 to enhance the efficacy of radiotherapy. [Read the Full Post]

Discovery of ASP5878: Synthesis and structure-activity relationships of pyrimidine derivatives as pan-FGFRs inhibitors with improved metabolic stability and suppressed hERG channel inhibitory activity

72 | Dec 26 2023

ASP5878 (27) exhibits promising potential as a therapeutic candidate for treating bladder cancer by targeting FGFR3, boasting improved metabolic stability, minimal hERG channel inhibition, potent FGFR3 inhibition in vitro and in vivo, and favorable safety and pharmacokinetic profiles in preclinical models. [Read the Full Post]

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes

110 | Dec 24 2023

A study evaluating Cinnamomum verum and Brazilian green propolis extracts revealed their potent antibacterial and antibiofilm properties against multidrug-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa, showcasing biocompatibility with human cells and suggesting a promising alternative approach to combat these pathogens. [Read the Full Post]

E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways

85 | Dec 24 2023

E7050 demonstrates potent anti-tumor and anti-angiogenic effects by inhibiting VEGFR2 phosphorylation and downstream signaling pathways in endothelial cells, reducing neovessel formation in vitro and in vivo, and attenuating tumor growth and angiogenesis in a xenograft model, suggesting its promising potential as a therapeutic agent for cancer and angiogenesis-related disorders. [Read the Full Post]

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function

0 | Dec 17 2023

The study shows that small molecule tyrosine kinase inhibitors targeting Syk and BTK effectively inhibit essential platelet functions, such as adhesion, secretion, and aggregation, but exhibit differential effects on downstream signaling pathways and protein activities in platelets. [Read the Full Post]

Combined inhibition of FGFR4 and VEGFR signaling enhances efficacy in FGF19 driven hepatocellular carcinoma

66 | Dec 15 2023

The combination of Lenvatinib, a multi-kinase inhibitor, and FGFR4 inhibitor H3B-6527 demonstrates enhanced efficacy in treating FGF19-driven hepatocellular carcinoma by leveraging Lenvatinib's cell non-autonomous VEGFR activity, indicating a promising potential for clinical application. [Read the Full Post]

Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?

46 | Dec 14 2023

The presence of IGF2 protein in human spermatozoa influences the expression of mitogens and reproductive hormones in Sertoli cells, indicating a paracrine regulatory mechanism that impacts gonocyte proliferation and spermatogonial fate during spermatogenesis. [Read the Full Post]

Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?

0 | Dec 14 2023

The presence of IGF2 protein in human spermatozoa influences the expression of mitogens and reproductive hormones in Sertoli cells, indicating a paracrine regulatory mechanism that impacts gonocyte proliferation and spermatogonial fate during spermatogenesis. [Read the Full Post]

Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?

0 | Dec 14 2023

The presence of IGF2 protein in human spermatozoa influences the expression of mitogens and reproductive hormones in Sertoli cells, indicating a paracrine regulatory mechanism that impacts gonocyte proliferation and spermatogonial fate during spermatogenesis. [Read the Full Post]

Lack of pharmacokinetic interaction between derazantinib and naringin in rats

67 | Dec 14 2023

The study validated a sensitive UPLC-MS/MS method for measuring derazantinib concentration in rat plasma, revealing that co-administration of derazantinib with naringin did not significantly alter its pharmacokinetic parameters, suggesting a safe concomitant use without requiring dose adjustment. [Read the Full Post]

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor

162 | Dec 12 2023

In this study, a series of EPHA2 kinase inhibitors, including derivatives of NVP-BHG712 and triazine-based compounds, were synthesized and evaluated, revealing eight inhibitors with low-nanomolar affinities (KD <10 nM) that demonstrated promising effects in controlling human colon carcinoma, highlighting their potential as therapeutic tools in cancer research. [Read the Full Post]

Supervised screening of Tecovirimat-like compounds as potential inhibitors for the monkeypox virus E8L protein

136 | Dec 10 2023

The study utilized computational methods and machine learning-guided screening to identify five promising drugs, ABX-1431, Alflutinib, Avacopan, Caspitant, and Darapalib, which effectively engage the MPXV E8L surface binding protein with higher affinity than Tecovirimat, potentially offering new avenues for the development of personalized treatments for Monkeypox virus infections. [Read the Full Post]

PI3K pathway mutation predicts an activated immune microenvironment and better immunotherapeutic efficacy in head and neck squamous cell carcinoma

43 | Dec 10 2023

*PI3K pathway mutations in head and neck squamous cell carcinoma patients are associated with significantly extended overall survival and enhanced immunotherapeutic responses, indicating their potential as a valuable biomarker for clinical prognosis and treatment outcomes.* [Read the Full Post]

The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells

132 | Dec 10 2023

The study reveals that AD80, a multikinase inhibitor, exerts potent antineoplastic effects in pancreatic cancer cells by inducing mitotic aberrations, DNA damage, autophagy, and apoptosis, providing crucial insights into potential targeted therapeutic strategies for this deadly disease. [Read the Full Post]

Single-cell RNA sequencing identifies an Il1rn+/Trem1+ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection

109 | Dec 08 2023

The study on thoracic aortic aneurysm and dissection (TAAD) utilizing single-cell RNA sequencing in a mouse model identified the Il1rn+/Trem1+ pro-inflammatory macrophage subpopulation as the predominant source of detrimental molecules, highlighting the potential of targeted therapy, specifically via Trem1 blockade, as a promising medical treatment for TAAD. [Read the Full Post]

Next-Generation Sequencing-Optimal Sequencing of Therapies in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

0 | Dec 04 2023

**This research paper provides a comprehensive overview of evidence-based sequencing of therapies in relapsed/refractory chronic lymphocytic leukemia (CLL) in the era of targeted drugs, emphasizing the importance of personalized treatment strategies and highlighting promising developments, such as noncovalent BTK inhibitors, while underscoring the urgent need for solutions in the challenging subgroup of patients previously exposed to both BTK and BCL2 inhibitors.** [Read the Full Post]

Transarterial chemoembolization with or without multikinase inhibitors for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis of randomized controlled trials

61 | Dec 04 2023

The systematic review and meta-analysis demonstrate that transarterial chemoembolization (TACE) combined with multikinase inhibitors (MKIs) significantly prolongs time to progression and improves objective response rates, but does not significantly impact overall or progression-free survival in patients with unresectable hepatocellular carcinoma, highlighting the importance of managing MKI-related toxicities in future clinical applications. [Read the Full Post]

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response

73 | Dec 01 2023

Targeting NR4A1 with OSI-930 may offer a promising therapeutic strategy for colon adenocarcinoma patients with high immune infiltration, pending rigorous clinical validation. [Read the Full Post]

Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies

149 | Dec 01 2023

Computational analyses identified acarbose as a potential inhibitor of the RapJ enzyme, crucial for inducing the sporulation pathway in Bacillus coagulans, but experimental validation is necessary to confirm its effectiveness. [Read the Full Post]

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice

102 | Dec 01 2023

A new study demonstrates that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation, indicating its potential as a therapeutic option for this condition. [Read the Full Post]

TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors

72 | Nov 29 2023

TRUST-II is a global phase II study evaluating taletrectinib's efficacy and safety in treating ROS1+ non-small-cell lung cancer and other ROS1+ solid tumors, with confirmed objective response rate as the primary endpoint and secondary endpoints including duration of response, progression-free survival, overall survival, and safety assessments, enrolling patients across North America, Europe, and Asia to address unmet needs in overcoming resistance, treating brain metastasis, and reducing neurological side effects. [Read the Full Post]

Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer

43 | Nov 29 2023

Increased autocrine production of EGF and TGF-α mediates both primary and acquired resistance to ALK and c-MET inhibitors in non-small-cell lung cancer, suggesting a potential therapeutic strategy involving combination treatments with EGFR inhibitors. [Read the Full Post]

Neutrophil-Specific Syk Expression Is Crucial for Skin Disease in Experimental Epidermolysis Bullosa Acquisita

59 | Nov 29 2023

Syk inhibition in neutrophils emerges as a pivotal therapeutic approach for epidermolysis bullosa acquisita, preventing skin disease triggered by anti-C7 antibodies and indicating potential treatment strategies. [Read the Full Post]

Inhibition of Mertk Signaling Enhances Bone Healing after Tooth Extraction

91 | Nov 29 2023

Targeting Mertk, a specific TAM receptor, enhances bone regeneration after tooth extraction, offering a potential therapeutic approach for improving outcomes in cases where the regenerative process is impaired. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

267 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity

78 | Nov 20 2023

Using advanced molecular dynamics simulations, researchers identified masitinib's stable hydrogen bond interactions with the Mpro enzyme, pinpointing the crucial role of His163, leading to the design of effective derivatives M3 and M4 with increased inhibitory efficiency against SARS-CoV-2. [Read the Full Post]

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells

264 | Nov 17 2023

Meticrane, a non-oncology drug originally used to treat hypertension, exhibits promising anti-cancer effects on leukemia and liver cancer cells, including synergistic interactions with epigenetic inhibitors, alterations in gene expression associated with non-cancer pathways, and considerable binding affinity to key cancer-related proteins, although it does not enhance the cytotoxicity of cytokine-induced killer cells, suggesting its potential as a novel cancer therapy warrants further investigation. [Read the Full Post]

Axin phosphorylation in condensates counteracts tankyrase-mediated degradation

72 | Nov 12 2023

The discovery of axin phosphorylation by casein kinase 1α within the tankyrase-binding site, hindering axin-tankyrase interaction and counteracting tankyrase-mediated degradation, represents a novel mechanism with implications for modulating Wnt signaling and potential cancer therapy. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

222 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

Circulating small extracellular vesicles promote proliferation and migration of vascular smooth muscle cells via AXL and MerTK activation

0 | Nov 07 2023

This study reveals that circulating small extracellular vesicles (csEVs) enhance the proliferation and migration of vascular smooth muscle cells (VSMCs) through phosphatidylserine (PS) interactions, and targeting the AXL and MerTK receptors may provide a viable approach for treating vascular diseases associated with neointima formation. [Read the Full Post]

Single-Nucleotide Polymorphism of the MLX Gene Is Associated With Takayasu Arteritis

71 | Nov 06 2023

The MLX-Q139R mutation in the MLX gene plays a crucial role in the pathogenesis of Takayasu arteritis by promoting inflammasome formation, increased oxidative stress, and impaired autophagy. [Read the Full Post]

Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer

37 | Nov 05 2023

This study reveals that the overexpression of Centromere protein O (CENPO) in lung adenocarcinoma is associated with a poor prognosis, and its involvement in immunosuppression and drug resistance highlights its potential as a prognostic biomarker and therapeutic target. [Read the Full Post]

Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates

0 | Nov 01 2023

The study demonstrated that the combination of the MET inhibitor merestinib with the FGFR inhibitor LY2874455 showed preliminary safety and biological activity, indicating the potential of targeting MET and FGFR pathways in the treatment of relapsed/refractory acute myeloid leukemia. [Read the Full Post]

Developments and challenges of FLT3 inhibitors in acute myeloid leukemia

72 | Oct 31 2023

FLT3 mutations are common in acute myeloid leukemia (AML) and targeting FLT3 has become a crucial part of AML treatment, although resistance to FLT3 inhibitors remains a challenge that is being addressed through the development of novel agents and multitarget strategies. [Read the Full Post]

CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway

119 | Oct 30 2023

CX3CL1 promotes migration and invasion of renal cell carcinoma (RCC) cells, potentially facilitating RCC metastasis to the spine, through activation of the Src/FAK signaling pathway. [Read the Full Post]

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

0 | Oct 30 2023

The study comprehensively evaluated histone modification status in cervical cancer patients, identifying a novel HMAG signature of nine histone modification-associated genes with strong prognostic value, offering crucial insights into prognosis prediction and tailored clinical treatments. [Read the Full Post]

The effectiveness of tivantinib for MET-high hepatocellular carcinoma: A protocol for meta analysis

67 | Oct 27 2023

The meta-analysis findings suggest that tivantinib does not appear to confer a significant benefit for the treatment of MET-high hepatocellular carcinoma, and it is associated with an increased risk of grade ≥3 neutropenia and leukopenia. [Read the Full Post]

Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway

102 | Oct 20 2023

The study found that kaempferol (Kae) inhibits glioma cell proliferation, promotes apoptosis, and inhibits migration and invasion, potentially through targeting EGFR/SRC/STAT3 signaling, and synergizes with gefitinib (Gef) to enhance antitumor effects, suggesting its potential as a candidate drug or chemosensitizer in glioma therapy. [Read the Full Post]

Investigation of Fenebrutinib Metabolism and Bioactivation Using MS3 Methodology in Ion Trap LC/MS

66 | Oct 17 2023

Fenebrutinib, an orally available Bruton tyrosine kinase inhibitor, has been characterized through in silico and in vitro studies, elucidating its metabolites and reactive intermediates, which can aid in understanding its adverse effects and facilitate the development of safer drugs. [Read the Full Post]

Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival

107 | Oct 16 2023

The study identified erbB3, calmodulin, PIM kinases, and Src family members as potential therapeutic targets in MPNSTs and demonstrated that combinatorial therapies targeting these pathways are more effective in reducing proliferation and survival. [Read the Full Post]

A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer

73 | Oct 14 2023

Alofanib, a small-molecule allosteric extracellular FGFR2 inhibitor, showed acceptable tolerability and preliminary signs of clinical activity in heavily pretreated patients with advanced gastric cancer, with a recommended phase 2 dose of 350 mg/m2 administered 5 days on and 2 days off. [Read the Full Post]

PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis

130 | Oct 14 2023

Proline-rich tyrosine kinase 2B (PTK2B) plays a role in the pathogenesis of ulcerative colitis (UC) by promoting neutrophil migration and inhibiting mucosal inflammation, making it a potential therapeutic target for UC treatment. [Read the Full Post]

Olverembatinib Treatment in Pediatric Patients With Relapsed Philadelphia-Chromosome-Positive Acute Lymphoblastic Leukemia

155 | Oct 13 2023

In this study, olverembatinib demonstrated both safety and efficacy in children with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), including some achieving complete remission as a single agent. [Read the Full Post]

Transcranial direct current stimulation attenuates chronic pain in knee osteoarthritis by modulating BDNF/TrkB signaling in the descending pain modulation system

114 | Oct 12 2023

This hypothetical study suggests that upregulation of the BDNF/TrkB signaling in the descending pain modulation system may be involved in chronic pain associated with knee osteoarthritis (KOA) in rats, and transcranial direct current stimulation (tDCS) may alleviate this pain by inhibiting the BDNF/TrkB signaling pathway. [Read the Full Post]

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study

157 | Oct 09 2023

This study aimed to identify new ligands for the platelet-derived growth factor receptor (PDGFR) through screening of thousands of compounds, resulting in the selection of potential drugs and natural compounds with high affinity, providing valuable insights for the development of more effective treatments for PDGFR-related diseases. [Read the Full Post]

Effects of the factor Xa inhibitor rivaroxaban on the differentiation of endothelial progenitor cells

40 | Oct 08 2023

The study demonstrated that rivaroxaban treatment increased the differentiation ability of vascular endothelial progenitor cells (EPCs), suggesting its potential for improving vascular repair in patients with coronary artery disease. [Read the Full Post]

Cell surface ATP synthase-released H+ and ATP play key roles in cocoa butter intake-mediated regulation of gut immunity through releases of cytokines in rat

105 | Oct 06 2023

Cocoa butter intake regulates gut immunity by increasing lymph flow, cell density, and the release of IL-1β, IL-6, and IL-10 in mesenteric lymph, with the involvement of macrophages, cell surface ATP synthase, and pH-dependent cytokine release. [Read the Full Post]

Myricetin: A Potent Anti-Amyloidogenic Polyphenol against Superoxide Dismutase 1 Aggregation

93 | Oct 04 2023

Myricetin, a plant flavonoid, has demonstrated potent inhibitory effects on SOD1 aggregation in ALS through a combination of molecular dynamics simulations and experimental observations, suggesting its potential as a therapeutic inhibitor for the disease. [Read the Full Post]

Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis

0 | Oct 02 2023

This study revealed that Lassa virus enters human cells via a unique macropinocytosis-related pathway involving dystroglycan, and identified cellular kinases, including human hepatocyte growth factor receptor (HGFR), as potential targets for antiviral therapy. [Read the Full Post]

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming

0 | Oct 02 2023

This study reveals that targeting FGFR1 and mTOR in combination can overcome drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) by inhibiting ATF4-mediated amino acid metabolic reprogramming. [Read the Full Post]

Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

0 | Oct 02 2023

This review discusses the concept of relapsed chronic lymphocytic leukemia (CLL), available treatment options, and emerging therapies, emphasizing the need for individualized therapy selection and the ongoing research in this field. [Read the Full Post]

Safety and tolerability of oral vorolanib for neovascular (wet) age-related macular degeneration: a phase I, open-label study

82 | Oct 01 2023

The study demonstrated that oral vorolanib improved visual outcomes in participants with neovascular age-related macular degeneration (nAMD) while maintaining a manageable safety profile. [Read the Full Post]

Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

57 | Sep 30 2023

This review examines the recent advancements in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), including targeted therapies, chimeric antigen receptor (CAR) T cell therapy, and the role of measurable residual disease (MRD) assessment, providing insights into therapeutic options and considerations for individualized treatment selection. [Read the Full Post]

Real-World Treatment Outcomes of MET Exon14 Skipping in Non-small Cell Lung Cancer: GFPC 03-18 Study

66 | Sep 29 2023

The real-life study found no evidence of a survival benefit with anti-MET tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (aNSCLC) and MET exon14 skipping mutations (METexon14). [Read the Full Post]

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming

57 | Sep 29 2023

This study demonstrates that targeting FGFR1 in human T-cell acute lymphoblastic leukemia (T-ALL) is a potential therapeutic strategy, but the development of resistance to FGFR1 inhibitors is mediated by ATF4-mediated amino acid metabolic reprogramming, which can be overcome by synergistically inhibiting FGFR1 and mTOR. [Read the Full Post]

Diazoxide improves muscle function in association with improved dyslipidemia and decreased muscle oxidative stress in streptozotocin-induced diabetic rats

85 | Sep 27 2023

Diazoxide administration in diabetic rats improves muscle strength development, reduces fatigue, lowers cholesterol and triglyceride levels, and improves oxidative stress parameters, suggesting its potential as a therapeutic intervention for diabetes-related complications. [Read the Full Post]

Precious Gene: The Application of RET-Altered Inhibitors

178 | Sep 23 2023

The novel RET-specific inhibitors selpercatinib and pralsetinib, along with ongoing clinical trials of TPX-0046 and zetletinib, demonstrate promising efficacy and safety in the treatment of RET-altered cancers, addressing the limitations of previous multikinase inhibitors. [Read the Full Post]

Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFRCSTMLR mutant protein: molecular modeling and free energy approach

62 | Sep 20 2023

The study identified compound C_42 as a potential drug candidate with strong binding affinity, favorable structural characteristics, and promising potential as an EGFR inhibitor for cancer treatment. [Read the Full Post]

Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase

102 | Sep 18 2023

[18F]PTBTK3, a PET radiotracer based on a selective BTK inhibitor, demonstrates BTK-dependent tumor uptake in BTK-positive tumors, showing promise for the diagnosis and development of BTK-targeted therapies. [Read the Full Post]

Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

145 | Sep 18 2023

Remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, effectively inhibits the activation of basophils and mast cells induced by serum from chronic urticaria patients, regardless of their responsiveness to omalizumab treatment. [Read the Full Post]

BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study

110 | Sep 16 2023

The VEM-PLUS study found that combining vemurafenib with cytotoxic chemotherapy or RAF- or mTOR-targeting agents did not significantly improve overall survival or progression-free survival compared to vemurafenib monotherapy in patients with solid tumors harboring BRAF V600E mutations. [Read the Full Post]

Circulating small extracellular vesicles promote proliferation and migration of vascular smooth muscle cells via AXL and MerTK activation

0 | Sep 10 2023

This study demonstrates that circulating small extracellular vesicles (csEVs) enhance the proliferation and migration of vascular smooth muscle cells (VSMCs) via phosphatidylserine (PS) and activate AXL and MerTK signaling pathways, highlighting their crucial role in neointima formation and suggesting the potential of dual AXL/MerTK inhibitors as a therapeutic approach for vascular diseases. [Read the Full Post]

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

85 | Sep 09 2023

BI-4020, a noncovalent, wild-type EGFR sparing, macrocyclic TKI, demonstrates potent inhibition of EGFR variants including T790M and C797S, and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. [Read the Full Post]

Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy

64 | Sep 04 2023

Complement-dependent synaptic pruning by microglia is a key mechanism underlying the development of neuronal damage and cognitive dysfunction in sepsis-associated encephalopathy (SAE). [Read the Full Post]

Evaluation of the Cytochrome P450 3A and P-glycoprotein Drug-Drug Interaction Potential of Futibatinib

49 | Sep 01 2023

Futibatinib, an FGFR1-4 inhibitor, should not be concomitantly used with dual P-gp and strong CYP3A inhibitors/inducers but can be administered alongside other drugs metabolized by CYP3A, as demonstrated in phase I studies. [Read the Full Post]

BTK Inhibitors in the Frontline Management of Waldenström Macroglobulinemia

84 | Aug 27 2023

BTK inhibitors, such as ibrutinib and zanubrutinib, have shown promising results in both treatment-naïve and relapsed/refractory Waldenström macroglobulinemia (WM) patients, with improved response rates and prolonged progression-free survival. [Read the Full Post]

How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists

0 | Aug 27 2023

This paper aims to provide Canadian nurses and pharmacists with a comprehensive reference on dosing, co-administration, and adverse event management strategies for patients with indolent B-cell NHL or CLL undergoing treatment with BTK inhibitors, addressing the evolving treatment landscape and unique safety profiles of these agents. [Read the Full Post]

Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines

99 | Aug 26 2023

Zanubrutinib, a small molecule Bruton's tyrosine kinase (BTK) inhibitor, has shown potential as an inhibitor of the HER2 signaling pathway and a candidate for repurposing in HER2-positive breast cancer. [Read the Full Post]

Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors

129 | Aug 26 2023

AZD3229 is a potent and selective small-molecule inhibitor with the potential to be a best-in-class treatment for a broad range of primary and imatinib-resistant secondary mutations in gastrointestinal stromal tumor (GIST). [Read the Full Post]

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors

79 | Aug 26 2023

On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion, making it the first tissue-agnostic targeted therapy for RET alterations. [Read the Full Post]

SEOM-GEIS clinical guideline for gastrointestinal stromal tumors (2022)

130 | Aug 24 2023

The Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) recommend a multidisciplinary approach and centralized management in reference centers for the diagnosis and treatment of gastrointestinal stromal tumor (GIST) patients. [Read the Full Post]

Ripretinib in advanced gastrointestinal stromal tumors: an overview of current evidence and drug approval

93 | Aug 24 2023

Ripretinib, a switch-control tyrosine kinase inhibitor, has shown promise in targeting both primary and secondary KIT and PDGFRα resistance mutations, making it a valuable therapeutic option in the management of advanced gastrointestinal stromal tumors (GISTs) that have developed resistance to imatinib and other treatments. [Read the Full Post]

Precision Targeted Therapy with BLU-667 for RET-Driven Cancers

83 | Aug 22 2023

BLU-667, a highly potent and selective RET inhibitor, has demonstrated significant inhibition of RET signaling and induced durable clinical responses in patients with RET-altered NSCLC and MTC, validating its potential as a targeted therapy for these cancers. [Read the Full Post]

Molecular basis and targeted therapy in thyroid cancer: Progress and opportunities

117 | Aug 21 2023

Thyroid cancer management has advanced with the development of targeted therapies, such as multi-tyrosine kinase inhibitors and immune checkpoint inhibitors, offering potential options for controlling tumor progression and addressing resistance mechanisms. [Read the Full Post]

Preclinical Evaluation of SCC244 (Glumetinib), a Novel, Potent, and Highly Selective Inhibitor of c-Met in MET-dependent Cancer Models

126 | Aug 20 2023

SCC244, a novel and highly selective inhibitor of c-Met kinase, demonstrated potent antitumor activity in preclinical studies, inhibiting c-Met signaling and suppressing neoplastic phenotypes in tumor and endothelial cells, suggesting its potential as a therapeutic agent for tumors with c-Met pathway alterations. [Read the Full Post]

Switch type I to type II TRK inhibitors for combating clinical resistance induced by xDFG mutation for cancer therapy

112 | Aug 16 2023

Compound 12d demonstrated potent inhibitory activity against various TRK fusion proteins, including those associated with acquired resistance to first-generation inhibitors, suggesting its potential as a lead compound for the treatment of TRK-driven cancers. [Read the Full Post]

BDNF and its signaling in cancer

0 | Aug 16 2023

BDNF signaling plays a significant role in cancer progression, and targeted therapies aimed at inhibiting BDNF and its associated pathways hold promise as potential therapeutic approaches. [Read the Full Post]

Anti-tumor efficacy of the novel KIT inhibitor IDRX-42 (formerly M4205) in patient- and cell line-derived xenograft models of gastrointestinal stromal tumor (GIST)

68 | Aug 11 2023

The study found that IDRX-42, a novel selective KIT inhibitor, exhibited significant antitumor activity by inducing tumor volume shrinkage, reducing mitotic activity, and causing characteristic myxoid degeneration in GIST xenograft models with specific KIT mutations. [Read the Full Post]

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib

124 | Aug 11 2023

This study proposes the use of AI-designed gamma-tocotrienol (AIGT) as a potential therapeutic option for chronic myeloid leukemia (CML) by targeting the BCR-ABL1 fusion protein, exhibiting promising efficacy and potential hepatoprotective properties compared to existing medications. [Read the Full Post]

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With At Least 2 Tyrosine Kinase Inhibitors

150 | Aug 11 2023

Asciminib, an allosteric high-affinity tyrosine kinase inhibitor, received marketing authorization from the European Commission for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase after evaluating its clinical efficacy and safety in the phase III ASCEMBL study. [Read the Full Post]

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling

42 | Aug 10 2023

The study revealed that the combination therapy targeting FGFR4 and EZH2 inhibitors synergistically induced apoptosis and inhibited hepatocellular carcinoma (HCC) development, highlighting its potential as a promising therapeutic strategy for HCC treatment. [Read the Full Post]

Integration of Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy into Model-Informed Dose Selection in Oncology First-in-Human Study: A Case of Roblitinib (FGF401)

98 | Aug 10 2023

The paper presents a comprehensive modeling and simulation framework that integrates pharmacometrics and statistical methods to inform dose selection of FGF401, a selective FGFR4 inhibitor, in oncology early clinical development, utilizing pharmacokinetic, pharmacodynamic, safety, and efficacy data. [Read the Full Post]

A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma

133 | Aug 08 2023

The combination of GSK2256098 and trametinib did not show significant clinical benefit in advanced pancreatic ductal adenocarcinoma (PDAC) patients, with short median progression-free survival and overall survival observed in the study. [Read the Full Post]

A phase Ib/II study of BLU-554, a fibroblast growth factor receptor 4 inhibitor in combination with CS1001, an anti-PD-L1, in patients with locally advanced or metastatic hepatocellular carcinoma

89 | Aug 07 2023

The preliminary trial results indicate that combining BLU-554 and CS1001 is a safe and effective treatment option for patients with locally advanced or metastatic hepatocellular carcinoma (HCC), with a 50% objective response rate and 100% disease control rate observed. [Read the Full Post]

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC

116 | Aug 07 2023

The study revealed that elevated expression of E74-like factor 4 (ELF4) in colorectal cancer is associated with increased metastasis and poor prognosis, and targeting the ELF4-related positive feedback circuit may offer a novel therapeutic approach. [Read the Full Post]

Successful Treatment and Retreatment With Erdafitinib for a Patient With FGFR3-TACC3 Fusion Squamous NSCLC: A Case Report

183 | Aug 01 2023

This case report demonstrates the potential efficacy of erdafitinib, an FGFR inhibitor, in achieving disease control and radiographic response in a patient with FGFR3-TACC3 fusion squamous NSCLC, suggesting the need for further investigation and expanding therapeutic options. [Read the Full Post]

Current scenario of pyrazole hybrids with in vivo therapeutic potential against cancers

163 | Aug 01 2023

This review provides a comprehensive overview of the potential of pyrazole hybrids as anticancer agents, summarizing their mechanisms of action, toxicity, and pharmacokinetics, with the aim of facilitating the rational exploitation and development of more effective candidates for cancer therapy. [Read the Full Post]

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence

84 | Jul 31 2023

This literature review examines the risks and safety of combining radiotherapy with anti-HER2 therapies in breast cancer, suggesting that monoclonal antibodies and checkpoint inhibitors can be safely combined with radiation, while caution is warranted for tyrosine kinase inhibitors and antibody-drug conjugates due to limited evidence. [Read the Full Post]

Inhibition of LAR attenuates neuroinflammation through RhoA/IRS-1/Akt signaling pathway after intracerebral hemorrhage in mice

80 | Jul 24 2023

This study revealed that leukocyte common antigen-related phosphatase (LAR) contributes to neuroinflammation after intracerebral hemorrhage (ICH) via the RhoA/IRS-1 pathway, and the administration of an extracellular LAR peptide (ELP) may serve as a potential therapeutic strategy to attenuate LAR-mediated neuroinflammation following ICH. [Read the Full Post]

A narrative review from gut to lungs: non-small cell lung cancer and the gastrointestinal microbiome

177 | Jul 24 2023

The gut microbiome plays a crucial role in modulating the immune response and therapeutic outcomes in lung cancer, highlighting the potential for microbiome-based interventions to improve treatment efficacy. [Read the Full Post]

How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists

67 | Jul 19 2023

This paper provides Canadian nurses and pharmacists with a comprehensive reference guide on dosing, co-administration, and adverse event management strategies for patients with indolent B-cell NHL or CLL being treated with Bruton's tyrosine kinase (BTK) inhibitors. [Read the Full Post]

BET inhibition targets ABC-DLBCL constitutive B-cell receptor signaling through PAX5

54 | Jul 19 2023

The study demonstrates that combining the BET inhibitor AZD5153 with the Bruton tyrosine kinase inhibitor acalabrutinib enhances efficacy in ABC-DLBCL by targeting PAX5 and BCR signaling pathways, offering potential for improved treatment outcomes in relapsed or refractory patients. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

0 | Jul 15 2023

Myelofibrosis, a hematologic malignancy characterized by splenomegaly, is primarily treated with JAK inhibitors, although spleen size reduction is not consistent, and new pharmacotherapies and combination treatments are being explored to improve outcomes. [Read the Full Post]

Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms

147 | Jul 15 2023

The comprehensive profiling of four JAK2 inhibitors revealed their distinct clinical profiles, including differential effects on JAK-STAT signaling, inflammatory response, erythroid colony formation, leukemic engraftment, and iron regulation, providing valuable insights for personalized therapy in myeloproliferative neoplasm patients. [Read the Full Post]

Activity and safety of first-line treatments for advanced melanoma: A network meta-analysis

156 | Jul 14 2023

The systematic review and network meta-analysis revealed that relatlimab/nivolumab demonstrated similar progression-free survival and overall response rate to ipilimumab/nivolumab in the first-line treatment of advanced melanoma, with a potential advantage of a better safety profile. [Read the Full Post]

Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma

138 | Jul 08 2023

This study reports the identification of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer, expanding the spectrum of translocation partners and highlighting the importance of further investigation regarding the impact of dual NTRK3 fusion on TRK inhibitor therapy and prognosis. [Read the Full Post]

Larotrectinib versus historical standard of care in patients with infantile fibrosarcoma: protocol of EPI-VITRAKVI

143 | Jul 08 2023

The EPI VITRAKVI study is a retrospective study that compares the time to medical treatment failure between larotrectinib and chemotherapy in patients with infantile fibrosarcoma using external historical controls and adjusting for potential confounding using the Inverse Probability of Treatment Weighting method. [Read the Full Post]

Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS

98 | Jul 06 2023

RAS proteins, including KRAS, HRAS, and NRAS, function as GTPases and play crucial roles in cell signaling pathways involved in growth, division, and survival, with RAS mutations being common in various cancers, particularly KRAS mutations in lung, colorectal, and pancreatic cancers. [Read the Full Post]

AXL Inhibitor TP-0903 Reduces Metastasis and Therapy Resistance in Pancreatic Cancer

96 | Jul 02 2023

The study demonstrates that the AXL inhibitor TP-0903 exhibits anti-metastatic, antitumor effects, and sensitizes pancreatic ductal adenocarcinoma to therapy, potentially providing a new treatment strategy for pancreatic cancer. [Read the Full Post]

Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection

68 | Jul 02 2023

In this study, Axl kinase inhibitors demonstrated efficacy in reducing RSV infection, ameliorating pulmonary pathology, and promoting the expression of interferon-stimulated genes, suggesting their potential as broad-spectrum antiviral therapeutics. [Read the Full Post]

Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy

83 | Jun 28 2023

The study found that the cationic G4 PAMAM dendrimer formulation of erlotinib showed superior antiproliferative activity against A549 lung cells compared to neutral G5 dendrimers and erlotinib alone, suggesting its potential as a targeted and sustained-release carrier for lung cancer treatment. [Read the Full Post]

Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing

127 | Jun 28 2023

This case study showcases the efficacy of ex vivo drug testing using patient-derived tumor organoids as a precision medicine approach, leading to significant clinical improvement and prolonged stable disease in a patient with platinum-resistant, advanced low-grade serous ovarian cancer. [Read the Full Post]

Advances in clinical studies of FLT3 inhibitors in acute myeloid leukemia

97 | Jun 26 2023

This comprehensive review article examines the current status of FLT3 inhibitors in clinical research for acute myeloid leukemia (AML) patients and explores treatment strategies, including combination therapies, to overcome drug resistance and improve patient outcomes. [Read the Full Post]

Structural insights into the potency and selectivity of covalent pan-FGFR inhibitors

110 | Jun 24 2023

This study investigates the potency, selectivity, and ability to overcome gatekeeper mutations of covalent pan-FGFR inhibitors, providing valuable insights for the development of next-generation inhibitors with improved properties. [Read the Full Post]

[Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib]

74 | Jun 22 2023

Savolitinib, a specific tyrosine kinase inhibitor targeting the MET protein, has been approved in China for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations, and studies are ongoing to evaluate its efficacy in patients with other MET abnormalities. [Read the Full Post]

Molecular Docking, Molecular Dynamics Simulations, and Free Energy Calculation Insights into the Binding Mechanism between VS-4718 and Focal Adhesion Kinase

169 | Jun 21 2023

This research work elucidates the binding mechanism between VS-4718 and focal adhesion kinase (FAK), providing valuable insights for optimizing the design of FAK inhibitors in cancer therapy. [Read the Full Post]

An intuitionistic approach for the predictability of anti-angiogenic inhibitors in cancer diagnosis

108 | Jun 21 2023

This research employs the PROMETHEE-II decision-making algorithm and fuzzy models to rank and determine the most efficacious anti-angiogenesis inhibitors for cancer treatment based on the evaluation of growth factors and predefined criteria. [Read the Full Post]

Effect of insulin-like growth factor system on luteinising angiogenesis

112 | Jun 21 2023

This study found that while exogenous IGF1 and IGF2 had limited effects on luteinizing follicular angiogenesis and progesterone production, inhibiting the IGF1 receptor signaling significantly reduced endothelial cell growth and progesterone concentration, indicating its crucial role in these processes. [Read the Full Post]

Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response

113 | Jun 20 2023

The study revealed that transfection of specific microRNAs enhanced the sensitivity of malignant pleural mesothelioma cells to chemotherapy and a FAK inhibitor, while also demonstrating that YM155-resistant cells showed increased exosome secretion and upregulation of drug transporter genes ABCA6 and ABCA10, which correlated with poor sensitivity to YM155. [Read the Full Post]

Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia

180 | Jun 19 2023

The study demonstrates that sustained treatment with the JAK/TYK2 inhibitor cerdulatinib leads to JAK1 overexpression and enhanced JAK/STAT signaling in TYK2-rearranged ALL cells, but withdrawal of the drug reverses these effects, while histone deacetylase inhibitor (HDACi) therapies show efficacy against cerdulatinib-resistant cells, offering a potential alternative treatment approach for TYK2-rearranged B-ALL patients who have developed resistance to JAKi. [Read the Full Post]

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

125 | Jun 18 2023

Elevated expression of glycosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) is associated with poor survival, enhanced BCR pathway signaling, and increased phosphorylation of Bruton tyrosine kinase (BTK), highlighting its potential as an oncogenic factor and therapeutic target. [Read the Full Post]

From preclinical efficacy to 2022 updated CROWN trial, lorlatinib is the preferred 1st-line treatment of advanced ALK+ NSCLC

176 | Jun 14 2023

The data from the CROWN trial, including the sustained and durable responses, favorable 3-year progression-free survival rates, and manageable CNS adverse events, strongly support lorlatinib as the preferred treatment for advanced ALK+ NSCLC. [Read the Full Post]

GEF-H1 Transduces FcεRI Signaling in Mast Cells to Activate RhoA and Focal Adhesion Formation during Exocytosis

126 | Jun 13 2023

The study found that GEF-H1 acts as a signal transducer, activating RhoA and promoting mast cell spreading and exocytosis, thus playing a crucial role in antigen-stimulated mast cell activation. [Read the Full Post]

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial

73 | Jun 13 2023

The combination of entospletinib and decitabine showed limited efficacy with low complete remission rates and short overall survival in older patients with acute myeloid leukemia (AML) and specific genetic mutations or karyotype abnormalities. [Read the Full Post]

Glycolytic System in Axons Supplement Decreased ATP Levels after Axotomy of the Peripheral Nerve

57 | Jun 10 2023

The study demonstrates that the glycolytic system in both Schwann cells and axons is the main source of ATP maintenance in the distal nerve stump during Wallerian degeneration, highlighting its significance in neurologic therapies. [Read the Full Post]

Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma

161 | Jun 07 2023

Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis, and the limited efficacy of available therapies in patients with moderate liver dysfunction highlights the need for improved treatment algorithms and novel therapies specifically designed for this patient population. [Read the Full Post]

Discovery of Potent and Wild-Type-Sparing Fourth-Generation EGFR Inhibitors for Treatment of Osimertinib-Resistance NSCLC

127 | Jun 02 2023

The development of Osimertinib derivatives as fourth-generation inhibitors for the treatment of Osimertinib-resistant NSCLC, particularly the top candidate D51, shows promising selectivity and antitumor activity with favorable in vivo druggability. [Read the Full Post]

"RB-reactivator screening" as a novel cell-based assay for discoveries of molecular targeting agents including the first-in-class MEK inhibitor trametinib (trade name: Mekinist)

83 | May 27 2023

The RB-reactivator screening led to the discovery of novel molecular-targeting agents, including trametinib, which was approved as the first-in-class MEK inhibitor and selected as the Drug Discovery of the Year in 2013 by the British Pharmacological Society. [Read the Full Post]

MAPK Inhibition Requires Active RAC1 Signaling to Effectively Improve Iodide Uptake by Thyroid Follicular Cells

77 | May 27 2023

The present study suggests that potentiating RAC1 activity could enhance the recovery of NIS expression induced through MAPK pathway inhibition, providing new opportunities for therapeutic intervention in refractory differentiated thyroid carcinomas. [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

152 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

Tyrosine Kinase Inhibitors Target B Lymphocytes

243 | May 20 2023

Protein kinase inhibitors previously used to treat ALK-positive lung cancer cells have shown potential in targeting LTK-positive B cells, providing new treatment options for autoimmune disorders and blood cancers. [Read the Full Post]

Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates

169 | May 19 2023

The study provides preliminary evidence that the combination therapy with MET and FGFR inhibitors is a safe and biologically active treatment option for patients with relapsed/refractory acute myeloid leukemia. [Read the Full Post]

Structural, spectroscopic, luminescence sensing and TD-DFT theoretical studies of a CuP2N-type complex

130 | May 18 2023

The passage describes a heteroleptic cuprous complex with a CuP2N coordination triangle, which exhibits UV-Vis absorption due to LLCT characteristic excited states and luminescence light-up sensing for pyridine in a paper-based film. [Read the Full Post]

Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach

80 | May 17 2023

This study found that low BBOX1 expression in clear cell renal cell carcinoma (RCC) patients is associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils, and identified potential drugs, including midostaurin, that can inhibit RCC cells with low BBOX1 expression. [Read the Full Post]

Ocular adverse events associated with BRAF and MEK inhibitor combination therapy: a pharmacovigilance disproportionality analysis of the FDA adverse event reporting system

131 | May 17 2023

The authors conducted a retrospective study using FAERS data to investigate oAEs associated with three BRAF and MEK inhibitor combination therapies, identifying both previously reported and new oAEs and noting that oAE profiles varied across treatment regimens. [Read the Full Post]

ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer

127 | May 17 2023

The ANCHOR CRC study showed that the first-line combination of encorafenib + binimetinib + cetuximab was effective and safe in treating BRAFV600E-mutated metastatic colorectal cancer patients with a locally assessed confirmed objective response rate of 47.4%. [Read the Full Post]

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models

128 | May 16 2023

UBX-382 is a potent and orally available PROTAC that effectively targets both wild-type and mutant BTK proteins to inactivate B-cell receptor signaling, leading to complete tumor regression in murine xenograft models within 2 weeks of oral dosing. [Read the Full Post]

A phase I/II study of epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer

150 | May 15 2023

This study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of daily oral epertinib combined with trastuzumab, vinorelbine, or capecitabine in patients with pre-treated HER2-positive metastatic breast cancer, with promising results. [Read the Full Post]

Investigation of the relationship between betatrophin and certain key enzymes involved in carbohydrate and lipid metabolism in insulin-resistant mice

105 | May 15 2023

The study found that insulin resistance increased betatrophin expression and serum levels, but did not correlate with the expression of LDH5, ACC1, and CS enzymes in mice. [Read the Full Post]

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

93 | May 14 2023

The ASCEMBL study evaluated the health-related quality of life of patients with chronic myeloid leukemia in chronic phase treated with asciminib and showed stable CML symptoms and HRQOL with asciminib and a clinically meaningful increase in diarrhea severity with bosutinib. [Read the Full Post]

MET overexpression contributes to STAT4-PD-L1 signaling activation associated with tumor-associated, macrophages-mediated immunosuppression in primary glioblastomas

36 | May 14 2023

The study found that the dysregulated receptor tyrosine kinase MET and its interaction with the tumor microenvironment, specifically the MET-STAT4-PD-L1 axis and tumor-associated macrophages, may contribute to immune evasion in primary glioblastoma and are associated with poor prognosis. [Read the Full Post]

Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison

105 | May 14 2023

This study compared the effectiveness of mobocertinib, a novel EGFR tyrosine kinase inhibitor, with real-world treatments in platinum-pretreated patients with advanced EGFR ex20ins-mutant NSCLC, and found that mobocertinib provided substantially improved outcomes. [Read the Full Post]

Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer

59 | May 08 2023

The study provides evidence that the KLF5-EphA2 axis promotes stemness and drug resistance in basal-like breast cancer and targeting EphA2 may be a potential therapeutic strategy. [Read the Full Post]

Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study

140 | May 02 2023

The study shows that conversion chemotherapy followed by surgery and apatinib-targeted therapy combined with SOX chemotherapy may be beneficial for patients with advanced gastric cancer. [Read the Full Post]

ARRY-382 in Combination with Pembrolizumab in Patients with Advanced Solid Tumors: Results from a Phase 1b/2 Study

86 | Apr 18 2023

This study found that ARRY-382 plus pembrolizumab was well-tolerated but provided limited clinical benefit in patients with advanced solid tumors. [Read the Full Post]

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

171 | Apr 11 2023

The study investigates the role of nerve growth factor and its receptor, tropomyosin receptor kinase A, in triple-negative breast cancer and suggests that targeting TrkA may be a potential therapeutic strategy for this disease. [Read the Full Post]

Circulating small extracellular vesicles promote proliferation and migration of vascular smooth muscle cells via AXL and MerTK activation

69 | Apr 08 2023

The study investigated the role of circulating small extracellular vesicles (csEVs) in vascular smooth muscle cell (VSMC) functions and neointima formation after vascular injury, demonstrating that csEVs enhance VSMC proliferation and migration via membrane phosphatidylserine (PS) and activate AXL and MerTK signaling pathways, and dual AXL/MerTK inhibition may be a potential treatment for vascular diseases. [Read the Full Post]

Integrated profiling uncovers prognostic, immunological, and pharmacogenomic features of ferroptosis in triple-negative breast cancer

59 | Apr 08 2023

The study explores the role of ferroptosis in TNBC, identifying different patterns of ferroptosis associated with prognostic and immunological traits, proposing a ferroptosis-relevant scoring system, and predicting small-molecule agents for high-risk patients. [Read the Full Post]

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

297 | Apr 05 2023

This research demonstrates that mutations in the K-D-K-E methyltransferase motif restrict the cell-to-cell spread of Newcastle disease virus via tunnelling nanotubes. [Read the Full Post]

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study

92 | Apr 05 2023

Capmatinib showed meaningful improvements in cough and preserved quality of life in patients with METex14-mutated advanced non-small cell lung cancer, as reported by patient-reported outcomes in the GEOMETRY mono-1 study. [Read the Full Post]

Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib

136 | Apr 05 2023

This retrospective medical record review study demonstrated that capmatinib is effective in treating non-small-cell lung cancer patients with MET exon 14 skipping mutation and brain metastases in a real-world setting, with high response rates and progression-free survival. [Read the Full Post]

Successful Treatment with Crizotinib to Overcome Drug Resistance Possibly Due to Mesenchymal-epithelial Transition Amplification in a Lung Cancer Patient with the Echinoderm Microtubule-associated Protein-like 4-anaplastic Lymphoma Kinase Fusion Gene

84 | Apr 04 2023

This case report highlights the potential effectiveness of crizotinib, a MET inhibitor, in ALK-positive lung cancer patients with MET amplification who have developed resistance to ALK-TKIs. [Read the Full Post]

Monitoring paxillin in astrocytes reveals the significance of the adhesion GPCR VLGR1/ADGRV1 for focal adhesion assembly

192 | Apr 04 2023

VLGR1 is a vital component of focal adhesions and regulates cell migration by controlling focal adhesion turnover during their assembly, and its dysfunctions may contribute to the pathogenesis of Usher syndrome, epilepsy, and other related diseases. [Read the Full Post]

A Novel Quantum Dots-Based Fluorescent Sensor for Determination of the Anticancer Dacomitinib: Application to Dosage Forms

107 | Apr 01 2023

The study proposes a novel spectrofluorimetric method for determining the concentration of dacomitinib using newly synthesized nitrogen-doped carbon quantum dots as fluorescent probes, which exhibit native fluorescence and are selectively quenched by increasing concentrations of dacomitinib, offering a simple, efficient, and eco-friendly means of determining the concentration of dacomitinib. [Read the Full Post]

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis

186 | Apr 01 2023

Fedratinib is a selective JAK2 inhibitor that has been approved by the FDA for the treatment of intermediate-2 or high-risk primary or secondary MF, providing a second-line treatment option for patients who failed or discontinued ruxolitinib, but new combinations with other targeted therapies are needed to improve management of the disease. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

197 | Apr 01 2023

Myelofibrosis is a hematologic malignancy characterized by splenomegaly in most patients, with JAK inhibitors being the primary pharmacologic treatment option, but alternative therapies and non-pharmacologic approaches may also be considered, and novel combination therapies are being explored. [Read the Full Post]

New therapies in non-small cell lung cancer with EGFR exon 20 insertion mutations

123 | Mar 31 2023

The review identified promising therapies for NSCLC with EGFR exon 20 insertion mutations, but further comparative studies with larger sample sizes and better design are needed to confirm their efficacy. [Read the Full Post]

Contact Sensitization and Phototoxic and Photoallergic Potential of Tirbanibulin 1% Ointment in Healthy Volunteers

67 | Mar 30 2023

The results of the three phase 1 studies suggest that tirbanibulin 1% ointment is safe for topical application in the treatment of actinic keratosis, without any evidence of sensitization or phototoxic or photoallergic potential in healthy adults. [Read the Full Post]

Inhibition of the epigenetically activated miR-483-5p/IGF-2 pathway results in rapid loss of meningioma tumor cell viability

102 | Mar 30 2023

The study found that targeting the autocrine miR-483/IGF-2 stimulation and IGF-2 pathway may provide a viable treatment option for meningioma. [Read the Full Post]

Identification of Inhibitors of Tubulin Polymerization Using a CRISPR-Edited Cell Line with Endogenous Fluorescent Tagging of β-Tubulin and Histone H1

107 | Mar 29 2023

The study presents a novel approach for identifying tubulin polymerization inhibitors using CRISPR-edited cells with fluorescently tagged endogenous β-tubulin and nuclear protein, enabling the screening of large compound libraries containing diverse chemical families for the discovery of new and effective therapies for cancer treatment. [Read the Full Post]

Identification of a novel circRNA-miRNA-mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis

121 | Mar 28 2023

This study explores the role of circRNAs in hepatocellular carcinoma and identifies potential diagnostic and therapeutic targets using various analytical methods. [Read the Full Post]

The outcome of ibrutinib-based regimens in relapsed/refractory central nervous system lymphoma and the potential impact of genomic variants

102 | Mar 28 2023

This study suggests that ibrutinib-based therapy is effective and safe for treating r/r CNSL patients, and patients with less genomic complexity, especially with regard to TMB, may benefit more from ibrutinib regimens. [Read the Full Post]

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report

101 | Mar 26 2023

This case report highlights the possibility of sustained response off therapy after discontinuing fostamatinib in chronic immune thrombocytopenia. [Read the Full Post]

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

259 | Mar 22 2023

This study identified the metabolomic profile and potential therapeutic effects of quercetin and its metabolites in cognitive impairment and Parkinson's disease, but further research is needed to confirm these findings in vivo and address potential adverse effects. [Read the Full Post]

Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion

245 | Mar 22 2023

This study found that a knee flexion angle of approximately 110 degrees is most effective in reducing vibration transmissibility during whole-body vibration exercise, while also observing a positive correlation between the rating of perceived exertion and the platform-to-head transmissibility. [Read the Full Post]

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

229 | Mar 21 2023

The research developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. [Read the Full Post]

WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation

130 | Mar 20 2023

WP1130 specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice. [Read the Full Post]

USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury

133 | Mar 20 2023

This study suggests that USP9x inhibition could be a potential therapeutic target for septic liver injury by promoting CD8+ T-cell function via autophagy regulation. [Read the Full Post]

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

225 | Mar 18 2023

The study identified PIM kinase as a potential target for the development of novel treatments for alveolar echinococcosis, and demonstrated the utility of high-throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. [Read the Full Post]

High-Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood-Spinal Cord Barrier Protection

81 | Mar 18 2023

The study developed a high-throughput screening assay to identify candidate drugs that protect the blood-brain spinal cord barrier function and demonstrated the neuroprotective effect of berberine and mubritinib after spinal cord injury. [Read the Full Post]

Mubritinib enhanced the inhibiting function of cisplatin in lung cancer by interfering with mitochondrial function

64 | Mar 18 2023

Mubritinib can target mitochondrial electron transport chain complexes and disrupt mitochondrial function, ultimately inducing oxidative stress and increasing ROS levels, leading to its antitumor effect in lung cancer. [Read the Full Post]

Targeting fibroblast growth factor receptors causes severe craniofacial malformations in zebrafish larvae

114 | Mar 16 2023

The study investigated the effects of mutated fgfr2 sa10729 allele in zebrafish on cartilage and bone formation, and found that pharmacological targeting of FGFR1-4 kinase signaling causes severe craniofacial malformations, while abrogation of FGFR2 kinase signaling alone does not induce craniofacial skeletal abnormalities. [Read the Full Post]

Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer

72 | Mar 15 2023

The study demonstrated the potential immune regulatory role of DVL2 proteins in HER2+ breast cancer, and suggested further investigation of DVL paralogs as potential therapeutic targets. [Read the Full Post]

Role of pericytes in the development of cerebral cavernous malformations

99 | Feb 25 2023

Pericytes in cerebral cavernous malformation (CCM) are essential for lesion development and fibronectin intervention may provide a novel target for therapeutic intervention, as pericyte function inhibition and increased fibronectin expression were found to be linked to CCM lesion development. [Read the Full Post]

Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation

135 | Feb 24 2023

This study found that MEK5 is aberrantly expressed in clear cell renal cell carcinoma, activating the mTOR signaling pathway, and inhibiting MEK5 using BIX02189 shows promise as a new therapeutic strategy for ccRCC. [Read the Full Post]

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

138 | Feb 22 2023

A young patient with relapsed/refractory Ph-like ALL was successfully treated with chimeric antigen receptor T (CAR-T) cells after bridging with compassionate-use ponatinib and low-dose prednisone, and maintained with low-dose ponatinib, resulting in measurable residual disease negativity and B-cell aplasia 20 months later, marking this as the first reported use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

453 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Small Bowel Lipomatosis: An Unusual Radiological Finding in Patients With Renal Cell Cancer on Pazopanib

71 | Feb 06 2023

The study found that small bowel lipomatosis is a unique finding in patients with advanced renal cell carcinoma receiving pazopanib, but is not seen with other tyrosine kinase inhibitors. [Read the Full Post]

Addressing adherence to guidelines on prevention of acute chemotherapy-induced nausea and vomiting in pediatric patients

181 | Feb 04 2023

Guideline adherence for prevention of chemotherapy-induced nausea and vomiting improved significantly, particularly in the high emetogenic chemotherapy group, with education, addition of anti-emetics to formulary, and implementation of a standardized guideline tool, but further improvement is needed in the moderately emetogenic chemotherapy group. [Read the Full Post]

Antiemetic use and chemotherapy induced nausea and vomiting related hospitalization costs after highly or moderately emetogenic chemotherapy

193 | Feb 04 2023

PrecisionQ's database analysis found lower CINV related hospitalization costs among patients receiving netupitant/fosnetupitant with palonosetron (NEPA) compared to aprepitant/fosaprepitant with ondansetron (APON) or aprepitant/fosaprepitant with palonosetron (APPA) during highly emetogenic chemotherapy or moderately emetogenic chemotherapy. [Read the Full Post]

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial

120 | Feb 03 2023

A study of 45 patients with metastatic colorectal cancer treated with regorafenib found that KRAS mutations in tissue or plasma did not impact its efficacy, but higher levels of circulating cell-free DNA were associated with poorer prognoses. [Read the Full Post]

Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

91 | Feb 02 2023

The treatment landscape for advanced hepatocellular carcinoma (HCC) has become complex with the introduction of immune checkpoint inhibitors (ICIs), and a number of second-line therapies, with rechallenge with ICIs being an attractive alternative, but requires careful evaluation and the identification of predictive biomarkers is an urgent matter to address in HCC research. [Read the Full Post]

SS18-SSX drives CREB activation in synovial sarcoma

85 | Jan 24 2023

Magdalene Cyra et al. showed that CREB was phosphorylated and activated in SySa, accompanied by downstream target expression. [Read the Full Post]

VEGFR-TKI treatment for radiation-induced brain injury after gamma knife radiosurgery for brain metastases from renal cell carcinomas

82 | Jan 23 2023

Ryuichi Noda et al. demonstrated the therapeutic effects of vascular endothelial growth factor receptor tyrosine kinase inhibitors on radiation-induced brain injury in patients with brain metastases from renal cell carcinoma treated via gamma knife radiosurgery. [Read the Full Post]

Treatment and Implications of Vascular Endothelial Growth Factor Inhibitor-Induced Blood Pressure Rise: A Clinical Cohort Study

113 | Jan 22 2023

Daan C H van Dorst et al. thought that both calcium channel blockers and renin-angiotensin system inhibitors were effective antihypertensive treatments. [Read the Full Post]

Preclinical Evaluation of Trabectedin in Combination With Targeted Inhibitors for Treatment of Metastatic Uveal Melanoma

90 | Jan 18 2023

Kseniya Glinkina et al. found that trabectedin alone or in combination with cabozantinib inhibited tumor growth in PDX UM mouse models. [Read the Full Post]

Integrated bioinformatics analysis and experimental validation reveals fatty acid metabolism-related prognostic signature and immune responses for uterine corpus endometrial carcinoma

117 | Jan 18 2023

Chenrui Guo et al. found that a FAMGs-based risk signature might be considered as an independent prognostic indicator to predict UCEC prognosis. [Read the Full Post]

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

125 | Jan 17 2023

Tingting Zhao et al.revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment. [Read the Full Post]

Integrative analysis reveals clinically relevant molecular fingerprints in pancreatic cancer

135 | Jan 17 2023

Libin Song et al. found that PCCLs with mutations in CDKN2A, TP53, and SMAD4 were more sensitive to certain anti-cancer drugs. [Read the Full Post]

IGF1R as a Potential Pharmacological Target in Allergic Asthma

80 | Jan 12 2023

Elvira Alfaro-Arnedo et al. demonstrated that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma. [Read the Full Post]

Crizotinib Nanomicelles Synergize with Chemotherapy through Inducing Proteasomal Degradation of Mutp53 Proteins

112 | Jan 10 2023

Tianxiang Yi et al. suggested a novel combination therapeutic strategy for targeting p53 cancer in further clinical application. [Read the Full Post]

Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas

142 | Jan 06 2023

Jingwei Yang et al. showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. [Read the Full Post]

Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs

163 | Jan 05 2023

Yinjiang Zhang et al. found that ferroptosis played a critical role in the diversity and complexity of the IS immune microenvironment. [Read the Full Post]

ZD6474 Attenuates Fibrosis and Inhibits Neovascularization in Human Pterygium by Suppressing AKT-mTOR Signaling Pathway

183 | Jan 05 2023

Wenting Liu et al. found that ZD6474 was more effective than MMC in reducing fibrosis and EMT in HPFs. [Read the Full Post]

Utilizing inner filter effect in resonance Rayleigh scattering technique: a case study with silver nanocubes as RRS probe and several analytes as absorbers

115 | Jan 04 2023

Rasoul Gheitaran et al. found that the newly developed IFE mechanism could be employed as an attractive and highly efficient analytical technique for measuring different analytes. [Read the Full Post]

Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma

120 | Jan 04 2023

Kohei Kobatake et al. thought that investigating RM on pre-treatment CT scans could effectively predict worse prognosis. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

0 | Jan 01 2023

C Dinkic et al. thought that pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. was a feasible regimen for patients with recurrent platinum-resistant EOC. [Read the Full Post]

Inhibition Ras/MEK/ERK pathway: An important mechanism of Baihu Jia Guizhi Decoction ameliorated rheumatoid arthritis

91 | Jan 01 2023

Qi Chen et al. found that the inhibition of Ras/MEK/ERK pathway was one of crucial mechanisms of BHJGZ for ameliorating synovitis of RA. [Read the Full Post]

Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

151 | Dec 31 2022

Karen E Anderson et al. explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients. [Read the Full Post]

Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib-Report of Three Cases

72 | Dec 31 2022

Erofili Papadopoulou et al. thought that gingival bleeding and MRONJ might develop as oral side effects of pazopanib use. [Read the Full Post]

Optimizing the value of lenalidomide maintenance by genetic profiling - an analysis of 556 Myeloma XI trial patients

182 | Dec 30 2022

Aikaterini Panopoulou et al. found that extended genetic profiling identified patients deriving exceptional benefit from Len maintenance. [Read the Full Post]

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy

168 | Dec 30 2022

Massimo Breccia et al. suggested that further efforts were needed to improve the therapeutic management of later lines of CML. [Read the Full Post]

Attenuated Dose Dasatinib in Newly Diagnosed Chronic Myeloid Leukemia Chronic Phase Patients in India

75 | Dec 29 2022

Rayaz Ahmed et al. thought that low dose dasatinib was safe and effective as an upfront therapy in CML-CP. [Read the Full Post]

Desensitization Protocol to Lenalidomide: An Effective and Safe Treatment Modality for Delayed Hypersensitivity-induced Rash in Patients with Multiple Myeloma

227 | Dec 29 2022

Oded Shamriz et al. thought that desensitization to lenalidomide was safe and effective. [Read the Full Post]

Combined use of dasatinib and quercetin alleviates overtraining-induced deficits in learning and memory through eliminating senescent cells and reducing apoptotic cells in rat hippocampus

121 | Dec 28 2022

Chenkang Wang found that D+Q alleviated overtraining-induced deficits in learning and memory through elimination of senescent cells and reduction of apoptotic cell number. [Read the Full Post]

Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients

124 | Dec 28 2022

Junyong Zou et al. validated that upregulations of hsa_circ_0030591 and hsa_circ_0040348 might play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker. [Read the Full Post]

GPR120-ERK1-Srebp1c signaling pathway regulates long-chain polyunsaturated fatty acids biosynthesis in marine teleost Siganus canaliculatus

82 | Dec 27 2022

Yewei Dong et al. found that the GPR120-ERK1-Srebp1c signaling pathway regulated rabbitfish LC-PUFA biosynthesis, representing a novel regulatory mechanism in vertebrates. [Read the Full Post]

Clinical impact of minimal residual disease and genetic subtypes on the prognosis of childhood acute lymphoblastic leukemia

153 | Dec 27 2022

Chih-Hsiang Yu et al. found that MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. [Read the Full Post]

Preformulation studies of dovitinib free base: Solubility, lipophilicity and stability

47 | Dec 26 2022

Suppakan Sripetch et al. found that dovitinib was most stable at pH 4 in the phosphate buffer species. [Read the Full Post]

Sulforaphane attenuates cancer cell-induced atrophy of C2C12 myotubes

84 | Dec 26 2022

Wenlan Li et al. suggested the chemoprotective and antioxidative function of SFN in myotubes, highlighting its therapeutic potential for cancer-related muscle wasting. [Read the Full Post]

Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984

67 | Dec 25 2022

Joseph W Kim et al. found that cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. [Read the Full Post]

DNA-Encoded Library Screening To Inform Design of a Ribonuclease Targeting Chimera (RiboTAC)

45 | Dec 25 2022

Samantha M Meyer et al. demonstrated that DEL could be used to identify compounds that bound and recruited proteins with effector functions in heterobifunctional compounds. [Read the Full Post]

A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer

238 | Dec 24 2022

Cong Zhang et al. developed a novel mitophagy-related gene signature that could be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients. [Read the Full Post]

Discovery of Clinical Candidate AZD0095, a Selective Inhibitor of Monocarboxylate Transporter 4 (MCT4) for Oncology

57 | Dec 24 2022

Frederick W Goldberg et al. thought that MCT4 inhibition might be of interest for immuno-oncology. [Read the Full Post]

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

196 | Dec 23 2022

Keiko Imamura et al. found that the treatment-responsive patients could be distinguished by lower levels of plasma NFL. [Read the Full Post]

Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: An analysis from the Italian pharmacovigilance database

122 | Dec 22 2022

Maria Antonietta Barbieri et al. suggested that more attention should be paid to the occurrence of serious life-threatening ADRs including respiratory failure, interstitial lung disease, and cardiogenic shock, especially in young patients. [Read the Full Post]

KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition

118 | Dec 22 2022

Yuanwang Pan et al identified KMT2D as a pivotal epigenetic modulator for LUSC oncogenesis and suggested that KMT2D loss renders LUSC therapeutically vulnerable to RTK-RAS inhibition. [Read the Full Post]

Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy

48 | Dec 21 2022

Mohammadsaleh Jahangir et al. offered a glimpse into the well-determined prognostic factor associated with the clinical response of RCC patients to PD-1/PD-L1 blockade therapy. [Read the Full Post]

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis

118 | Dec 20 2022

Rui Chen et al. thought that CLEC5A was a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy. [Read the Full Post]

Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status

47 | Dec 20 2022

Lucía Carril-Ajuria et al. found that no significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. [Read the Full Post]

Epigenomic and transcriptomic landscaping unraveled candidate repositioned therapeutics for non-functioning pituitary neuroendocrine tumors

79 | Dec 19 2022

B Aydin et al. found that molecular docking simulations, palbociclib, linifanib, trametinib, eplerenone, niguldipine, and zuclopenthixol showed higher binding affinities with hub genes compared to their inhibitors. [Read the Full Post]

Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion

51 | Dec 08 2022

Michael H Storandt et al. found that FGFR inhibitors, including pemigatinib, had shown promise in the management of CCA with FGFR2 fusion or rearrangement. [Read the Full Post]

The 8p11 myeloproliferative syndrome: Genotypic and phenotypic classification and targeted therapy

63 | Dec 08 2022

Taotao Li et al. thought that the TKIs might become an 8p11 treatment option as an alternative to hematopoietic stem cell transplantation. [Read the Full Post]

Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

157 | Dec 07 2022

Chengwei Zhang et al. found that MS4077 (5) and MS4078 (6) potently decreased cellular levels of oncogenic active ALK fusion proteins in a concentration- and time-dependent manner in SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells. [Read the Full Post]

Nanoplastics exposure induces vascular malformation by interfering with the VEGFA/VEGFR pathway in zebrafish (Danio rerio)

100 | Dec 04 2022

Lu Dai et al. found that nanoplastics might induce vascular malformation by regulating VEGFA/VEGFR pathway-related genes at the early developmental stage in zebrafish. [Read the Full Post]

Assessment of the Immune Response to Tumor Cell Apoptosis and Efferocytosis

136 | Dec 03 2022

Thomas A Werfel et al. described a model that enabled in vivo studies of tumor immunology in the aftermath of cytotoxic therapy with an emphasis on the impact of efferocytosis. [Read the Full Post]

Curcuminoids Inhibit Angiogenic Behaviors of Human Umbilical Vein Endothelial Cells via Endoglin/Smad1 Signaling

44 | Dec 03 2022

Yi-Fan Chou et al. suggested combination treatment with curcuminoids and a semaxanib was therefore expected to reverse semaxanib resistance. [Read the Full Post]

Update on diagnostic approaches and therapeutic strategies in systemic mastocytosis

84 | Nov 30 2022

Deepti H Radia et al. addressed the most topical questions related to diagnostics, classification, new disease entities, treatment and multiparameter prognostic scoring systems. [Read the Full Post]

Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro

122 | Nov 29 2022

Geoffrey A Pettitt et al. indicated a benefit from treatment interruptions or re-treatment following disease relapse in some patients. [Read the Full Post]

Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β-catenin mediated transduction of pro-osteogenic substrate

96 | Nov 26 2022

Otto J Juhl 4th et al. suggested that the observed β-catenin translocation is a result of focal adhesion turnover, providing evidence for a focal adhesion initiated, β-catenin mediated mechanism of substrate surface signal transduction. [Read the Full Post]

The efficacy and safety analysis of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma

41 | Nov 23 2022

Xiaoying Qian et al. thought that first-line immunotherapy had promising therapeutic potential in the treatment of PSC. [Read the Full Post]

Identification of biomarkers and key pathways in synovial sarcoma cells exposed to anlotinib by integrating bioinformatics analysis and experimental validation

74 | Nov 22 2022

Xiaoli Liu et al. identified biomarkers and key pathways associated with the effects of anlotinib treatment in SS cells. [Read the Full Post]

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

74 | Nov 12 2022

Iacopo Petrini et al. found that in combination with chemotherapy and lazertinib in NSCLCs who progressed on osimertinib (MARIPOSA-2). [Read the Full Post]

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

0 | Nov 12 2022

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs

84 | Nov 11 2022

Maan H Harbi et al. found that the Syk inhibitor R406 provided mild inhibition of platelet responses induced by atherosclerotic plaque and that this was mildly amplified by aspirin and ticagrelor. [Read the Full Post]

Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review

121 | Nov 04 2022

Christine Martineau et al. thought that adequate management of AEs associated with TRKi in adults should be a prime focus. [Read the Full Post]

Discovery and functional characterization of the oncogenicity and targetability of a novel NOTCH1-ROS1 gene fusion in pediatric angiosarcoma

125 | Nov 04 2022

Payal Jain et al. found that oral entrectinib treatment effectively suppressed the growth of NOTCH-ROS1-driven tumors. [Read the Full Post]

High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs

113 | Nov 04 2022

Doris Kafita et al. found that we could devise novel categorisation of patient tumours, treatment, and prognostic strategies. [Read the Full Post]

Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity

74 | Oct 27 2022

Yasir Y Elamin et al. found that poziotinib was active in EGFR exon 20-mutant NSCLC, although this activity was influenced by insertion location. [Read the Full Post]

HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies

85 | Oct 26 2022

Natalie F Uy et al. summarized recent progress in novel HER2-targeted agents, and projected next steps in advancing treatment for the thousands of patients with HER2 altered NSCLC. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

0 | Oct 25 2022

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseased mediated by osteoclasts. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Oct 25 2022

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

0 | Oct 20 2022

Cristina Zahonero et al. found that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status [Read the Full Post]

URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia

154 | Oct 19 2022

Patrick Miller-Rhodes et al. linked post-surgical endothelial activation, microglial MafB immunoreactivity, and synapse loss as key substrates for DSD, all of which could be prevented by URMC-099. [Read the Full Post]

Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases

61 | Oct 18 2022

Su'an Tang et al. provided a background on autoimmune diseases and provided an update on investigational SYK inhibitors. [Read the Full Post]

BDNF and its signaling in cancer

174 | Oct 07 2022

Mohammad Malekan et al. found that the aberrant signaling of BDNF was implicated in various cancers. [Read the Full Post]

ABCB1 and ABCG2 Control Brain Accumulation and Intestinal Disposition of the Novel ROS1/TRK/ALK Inhibitor Repotrectinib, While OATP1A/1B, ABCG2, and CYP3A Limit Its Oral Availability

129 | Oct 07 2022

Wenlong Li et al. found that systemic exposure of repotrectinib was substantially limited by CYP3A activity. [Read the Full Post]

Imatinib induces diastolic dysfunction and ventricular early-repolarization delay in the halothane-anesthetized dogs: Class effects of tyrosine kinase inhibitors

76 | Oct 03 2022

Koki Chiba et al. found that imatinib suppressed ventricular active relaxation and early repolarization, which might suggest the association of mitochondrial dysfunction-associated inhibition of ATP production. [Read the Full Post]

ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation

0 | Oct 02 2022

Yan Gu et al. found that ABHD5 interacted in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. [Read the Full Post]

Effects of natural 24-epibrassinolide on inducing apoptosis and restricting metabolism in hepatocarcinoma cells

99 | Sep 26 2022

Hongfei Zhou et al. suggested that EBR could be considered as a potential therapeutic compound for HCC due to its pro-apoptosis, restriction of energy metabolism, and other anti-cancer properties. [Read the Full Post]

Case Report of CCDC149-ALK fusion: a novel genetic alteration and a clinically relevant target in metastatic papillary thyroid carcinoma

57 | Sep 26 2022

Hannah Lee et al. recommend deep mutational sequencing in BRAFV600E-negative, RAIR PTC to identify targetable genetic alterations, including gene fusions, that might result in dramatic therapeutic benefits. [Read the Full Post]

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

103 | Sep 25 2022

Tongyue Zhang et al. uncovered functional and prognostic roles for ETV1 in HCC and exposed a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. [Read the Full Post]

An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors

74 | Sep 22 2022

Yingchao Sun et al. focused on the most recent literature that described the development of PDGFRA inhibitors and their use in clinical trials, as well as the potential benefits from different combination therapy strategies. [Read the Full Post]

Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics

120 | Sep 16 2022

Jingyuan Ya et al. found that effectively mitigate accumulation of senescent endothelial cells in cerebrovasculature might prevent age-related BBB dysfunction and might be of prophylactic or therapeutic value to extend lifelong health and wellbeing. [Read the Full Post]

Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition

120 | Sep 15 2022

Chenliang Zhang et al. demonstrated that in the early stage of proteasome inhibition, the maturation of the autophagosome was suppressed, which facilitated aggresome formation of misfolded proteins. [Read the Full Post]

Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment

46 | Sep 09 2022

Cuidi Li et al. found that the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment. [Read the Full Post]

Protein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML

59 | Sep 07 2022

Catana Allert et al. suggested that the leupaxin-PTK2B axis played an important role in acquired TKI resistance in AML. [Read the Full Post]

Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer

157 | Sep 06 2022

Yuhong Liu et al. thought that the combined use of tumor organoids and NGS was a potential way to test tumor heterogeneity and predict drug response in ER + BC, which contributed to the development of personalized therapy. [Read the Full Post]

Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

156 | Sep 05 2022

Christina Soeun Kwon et al. found EGFR exon 20 insertion mutations as the availability of new targeted treatments might offer additional therapeutic options to these patients. [Read the Full Post]

A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922

146 | Sep 05 2022

Melissa Schwab et al. found that the membrane Hsp70 density, but not cytosolic HSP levels determined the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in LDH-/- cells. [Read the Full Post]

Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs

136 | Sep 03 2022

Qiaohua Qin et al. found that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents. [Read the Full Post]

Differential prognostic impact of stratified additional chromosome abnormalities on disease progression among Malaysian chronic myeloid leukemia patients undergoing treatment with imatinib mesylate

104 | Aug 29 2022

Ismail Siti Mariam et al. concluded that the stratification based on individual ACAs had a differential prognostic impact and might be a potential novel risk predictive system to prognosticate and guided the treatment of CML patients at diagnosis and during treatment. [Read the Full Post]

Nintedanib Induces the Autophagy-Dependent Death of Gastric Cancer Cells by Inhibiting the STAT3/Beclin1 Pathway

68 | Aug 25 2022

Hui Zhu et al. showed that nintedanib could inhibit gastric cancer cells' proliferation and EMT process. [Read the Full Post]

FGF2 positively regulates osteoclastogenesis via activating the ERK-CREB pathway

106 | Aug 20 2022

Xin Wen et al. established the importance of FGF2 in bone homeostasis, hinting the potential use of FGF2/ERK/CREB specific inhibitors to fight against bone-related disorders, such as osteoporosis. [Read the Full Post]

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study

131 | Aug 17 2022

Reinhard Dummer et al. evaluated atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. [Read the Full Post]

Small Molecule Inhibitors of MERTK and FLT3 Induce Cell Cycle Arrest in Human CD8 + T Cells

80 | Aug 15 2022

Richard M Powell et al. found that caution was needed when using potent RTKIs in the context of antitumor immune responses. [Read the Full Post]

Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/Hedgehog signaling than that from normal bone

108 | Aug 15 2022

Tongtong Zhang et al. found that the activation of ERK and Hedgehog signaling pathway jointly enhanced the osteogenic potential of HO-ops to induce the formation of traumatic HO. [Read the Full Post]

A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML

86 | Aug 14 2022

Baohuan Cai et al. demonstrated a novel model for transformation of hematopoietic stem cells by chimeric FGFR1 kinases with the combined effects of direct protein activation by the full-length kinases and transcriptional regulation by the truncated nuclear tnFGFR1 derivative. [Read the Full Post]

Evaluation of the Efficacy of Saracatinib-Loaded Nanoparticles in Lymphatic Metastases of HNSCC with the Aid of Bioluminescence Imaging

84 | Aug 13 2022

Liwei Lang et al. showed great potential to evaluate treatments on metastatic diseases with the aid of bioluminescent technology. [Read the Full Post]

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline

131 | Aug 01 2022

Navneet Singh et al. thought that for patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib or lorlatinib. [Read the Full Post]

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

266 | Jul 30 2022

Pincha Devage Sameera Madushan Fernando et al. found that hesperidin showed therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis. [Read the Full Post]

Identification of Infigratinib as a Potent Reversible Inhibitor and Mechanism-Based Inactivator of CYP2J2: Nascent Evidence for a Potential In Vivo Metabolic Drug-Drug Interaction with Rivaroxaban

86 | Jul 20 2022

Lloyd Wei Tat Tang et al. reported that INF elicits potent reversible inhibition and MBI of CYP2J2. [Read the Full Post]

Compassionate Use of Ripretinib for Patients With Metastatic Gastrointestinal Stromal Tumors: Taiwan and Hong Kong Experience

247 | Jul 20 2022

Li-Ching Lin et al. thought that ripretinib was generally tolerable, with loss of hair being the most common AE. [Read the Full Post]

Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro

110 | Jul 19 2022

Takuya Kanke et al. suggested that FGFs, other than FGF8, exert suppressive effected on the cumulus expansion process in mice. [Read the Full Post]

Metastatic pulmonary carcinoids with EML4-ALK fusion response to ALK inhibitors: two case reports and review of literature

225 | Jul 18 2022

Xi Lei et al. recommend alectinib for the first-line treatment of metastatic PC with EML4-ALK fusion. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

0 | Jul 13 2022

Feng Li et al. demonstrated a significant merit of the method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy

76 | Jul 12 2022

Xiaoxue Xie et al. demonstrated that the bioactive nanovaccine dramatically enhanced antigen presentation by dendritic cells (DCs). [Read the Full Post]

Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab

212 | Jul 08 2022

Francesca Ligorio et al. thought that high CD36 expression predicted worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy. [Read the Full Post]

Type 1 Insulin-Like Growth Factor Receptor Nuclear Localization in High-Grade Glioma Cells Enhances Motility, Metabolism, and In Vivo Tumorigenesis

66 | Jul 06 2022

Ayelen Martin et al. provided evidence supporting the implications of the presence of IGF1R in the nucleus of glioma cells and a potential therapeutic opportunity for patients harboring gliomas with IGF1R nuclear localization. [Read the Full Post]

Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2 V617F driven cells

76 | Jul 06 2022

Jaqueline Cristina Fernandes et al. found that downregulation of JAK2/STAT signaling was an advantageous off-target effect of all three inhibitors. [Read the Full Post]

Reengineering Ponatinib to Minimize Cardiovascular Toxicity

288 | Jul 03 2022

Anna Pavlovna Hnatiuk et al. suggested that ponatinib cardiotoxicity was mediated by a few kinases, some of which were previously unassociated with cardiovascular disease. [Read the Full Post]

Caspase-3-induced activation of SREBP2 drives drug resistance via promotion of cholesterol biosynthesis in hepatocellular carcinoma

180 | Jul 01 2022

Etienne H Mok et al. demonstrated that CSC populations in HCC expanded via CASP3-dependent, SREBP2-mediated cholesterol biosynthesis in response to tyrosine kinase inhibitor therapy and that targeting cholesterol biosynthesis could overcome acquired drug resistance. [Read the Full Post]

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib

197 | Jun 27 2022

Fabio Scirocchi et al. reported that Cabozantinib might exert an immunostimulatory role by inducing immunogenic stress of prostate cancer cells and directly modulating dendritic cells (DCs). [Read the Full Post]

Survival benefit of using pemetrexed for EGFR mutation-positive advanced non-small-cell lung cancer in a randomized phase III study comparing gefitinib to cisplatin plus docetaxel (WJTOG3405)

158 | Jun 23 2022

Naoki Haratake et al. thought that pemetrexed should be administered without fail as a sequential treatment to improve the prognosis of EGFR-mutated NSCLC as well as like EGFR-tyrosine kinase inhibitors. [Read the Full Post]

Discovery of novel targets and mechanisms of MEK inhibitor Selumetinib for LGG treatment based on molecular docking and molecular dynamics simulation

128 | Jun 22 2022

Dongdong Zhang et al. thought that CDK2 might be a new direction of Selumetinib in the clinical treatment of LGG. [Read the Full Post]

The efficacy and safety of selumetinib as secondary therapy for late-stage and metastatic non-small cell lung cancer: results from a systematic review and meta-analysis

189 | Jun 21 2022

Wei-Wei Wang et al.showed that the efficacy of selumetinib was not superior compared to combined therapy for treating NSCLC but did have a better safety profile. [Read the Full Post]

BRAF V600E Mutation-Responsive miRNA-222-3p Promotes Metastasis of Papillary Thyroid Cancer Cells via Snail-Induced EMT

131 | Jun 16 2022

Yuan Gao et al. found miR-222-3p conduced more aggressive clinical manifestation of PTC by promoting Snail-induced EMT. [Read the Full Post]

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

254 | Jun 15 2022

Soei Gen et al. thought that osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion. [Read the Full Post]

Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis

186 | Jun 05 2022

Kehai Lin et al. thought that lorlatinib in never-smokers and low-dose alectinib in smokers could be considered optimal first-line therapy for advanced ALK-positive NSCLC. [Read the Full Post]

A Combination of Cytokine-Induced Killer Cells With PD-1 Blockade and ALK Inhibitor Showed Substantial Intrinsic Variability Across Non-Small Cell Lung Cancer Cell Lines

168 | Jun 03 2022

Yutao Li et al. supported the idea that combination therapies offer significant potential when they are optimized on a patient-by-patient basis. [Read the Full Post]

Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion

184 | Jun 02 2022

Xuehua Xie et al. described a case of MPM with CD74-ROS1 fusion who obtained complete and durable response after receiving crizotinib. [Read the Full Post]

Systemic Treatment Patterns and Outcomes in Patients With EGFR Mutated Non-small Cell Lung Cancer and Leptomeningeal Disease

217 | May 26 2022

Cristina M Merkhofer et.al found that prior exposure to osimertinib appeared to favorably influence the natural history of LM disease. [Read the Full Post]

Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancer With MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study

218 | May 22 2022

Manuel Weber et al. found that genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. [Read the Full Post]

CSF-1R inhibitor, pexidartinib, sensitizes esophageal adenocarcinoma to PD-1 immune checkpoint blockade in a rat model

416 | May 19 2022

Ashten N Omstead et al. showed limited toxicity with significant tumor shrinkage in pexidartinib treated animals compared to controls, single agent and in combination with a PD-1 inhibitor, AUNP-12. [Read the Full Post]

The BCL2 Inhibitor Venetoclax Plus Rituximab Is Active in MYD88 Wild-Type Polyneuropathy With Anti-MAG Antibodies

206 | May 18 2022

Chiara Briani et al. found that Class IV evidence that for a patient with relapsed anti-MAG antibody polyneuropathy, MYD88 wild-type, venetoclax plus rituximab was effective. [Read the Full Post]

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study

257 | May 09 2022

Kadir Eser et al. found that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. [Read the Full Post]

Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib

283 | May 08 2022

Yuki Takeyasu et al. showed that clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC. [Read the Full Post]

Regorafenib induces the apoptosis of gastrointestinal cancer-associated fibroblasts by inhibiting AKT phosphorylation

247 | May 07 2022

Mingjia Zhang et al. found that regorafenib inhibited the proliferation of CAFs and induced the apoptosis of CAFs in vitro. [Read the Full Post]

Tumor acidity/redox hierarchical-activable nanoparticles for precise combination of X-ray-induced photodynamic therapy and hypoxia-activated chemotherapy

344 | May 07 2022

Beibei Zhang et al. developed a combined therapeutic modality based on an intelligent nanosized platform (DATAT-NPVT) with tumor acidity-activated TAT presenting. [Read the Full Post]

How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review

305 | May 06 2022

Brigida Anna Maiorano et al. found that ICIs represented an effective option for pretreated advanced EC patients with a tolerable profile. [Read the Full Post]

FXR/ASS1 axis attenuates the TAA-induced liver injury through arginine metabolism

183 | May 03 2022

Weilong Hong et al. found that a protective role of the FXR/ASS1 axis in TAA-induced liver injury by targeting arginine metabolism, which might shed light on the development of novel therapeutic approaches for acute liver injury. [Read the Full Post]

FLT3 mutations in acute myeloid leukemia: a review focusing on clinically applicable drugs

268 | May 02 2022

Jae-Sook Ahn et al. summarized information on clinically available FLT3 inhibitors for the management of AML with FLT3 mutations. [Read the Full Post]

Unique Presentation of Bortezomib-Associated Thrombotic Microangiopathy Responsive to Therapeutic Plasma Exchange and Eculizumab Therapy

283 | Apr 27 2022

Robert C Sterner et al. demonstrated the possible utility of TPE with plasma replacement. [Read the Full Post]

Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers

355 | Apr 24 2022

Fabiana Ciciriello et al. proposed that the functional CFTR assay might guide personalized medicine in patients with CF-like clinical manifestations as well as in those carrying rare CFTR mutations. [Read the Full Post]

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium

208 | Apr 23 2022

Felix Reichel et al. found that the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc. [Read the Full Post]

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

445 | Apr 23 2022

Hidekatsu Nakai et al, found that the importance of achieving complete surgery and aiming for cure in the treatment of ovarian cancer and how the use of bevacizumab, olaparib, and niraparib should be individualized. [Read the Full Post]

Iguratimod Inhibits Skin Fibrosis by regulating TGF-β1/Smad Signaling Pathway in Systemic Sclerosis

363 | Apr 22 2022

Xi Xie et al. indicated T614 inhibited dermal fibroblasts activation and skin fibrosis at least partly by regulating TGF-β1/smad pathway in experimental SSc models and might be a promising therapeutic agent for SSc. [Read the Full Post]

A CT-based radiomics model to predict subsequent brain metastasis in patients with ALK-rearranged non-small cell lung cancer undergoing crizotinib treatment

431 | Apr 21 2022

Yongluo Jiang et al. developed a CT-based radiomics model to predict subsequent BM in patients with non-brain metastatic NSCLC undergoing crizotinib treatment. [Read the Full Post]

Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China

293 | Apr 18 2022

Wendao Li et al. found that the JAK inhibitors baricitinib and tofacitinib were promising therapeutic agents for patients with SAVI, AGS, and SPENCD, especially for the improvement of cutaneous lesions and febrile attacks. [Read the Full Post]

CDK4/6 inhibitor enhances the radiosensitization of esophageal squamous cell carcinoma (ESCC) by activating autophagy signaling via the suppression of mTOR

205 | Apr 17 2022

Wen-Jun Qin et al. found that palbociclib improved the radiosensitivity of ESCC in vivo and in vitro, and thus it might be a promising radiosensitization agent for the treatment of ESCC. [Read the Full Post]

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers

197 | Apr 14 2022

Maria Trovato thought that BM taxonomies should have common standards internationally recognized. [Read the Full Post]

Pharmacological Depletion of Microglia Leads to a Dose-Dependent Reduction in Inflammation and Senescence in the Aged Murine Brain

122 | Apr 11 2022

Milan R Stojiljkovic et al. found that increased and detrimental brain inflammation in aged murine brain could be impaired by selectively reducing the microglial cell population. [Read the Full Post]

Growth factor dependence of the proliferation and survival of cultured lacrimal gland epithelial cells isolated from late-embryonic mice

314 | Apr 02 2022

Yoko Karasawa et al. found that EGF and HGF might function in a cooperative autocrine manner, supporting cell proliferation and survival during LG development in late-embryonic and neonatal mice. [Read the Full Post]

Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial

309 | Mar 31 2022

Joyce F Liu et al. found that combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. [Read the Full Post]

Immune mechanisms of resistance to cediranib in ovarian cancer

329 | Mar 30 2022

Ganga Gopinathan et al. thought that combination of anti-IL-6 or anti-PD1 in patients might increase activity of VEGFR inhibitors and prolong disease-free survival. [Read the Full Post]

Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats

537 | Mar 27 2022

Ankit Uniyal et al. suggested that tozasertib mediates anti-nociceptive activity by inhibiting aurora kinase-mediated KIF17/mLin10/NR2B signaling. [Read the Full Post]

Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

499 | Mar 27 2022

On-Yu Hong 1 et al. showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells. [Read the Full Post]

New Approaches for the Synthesis of 2,3,5,6-Tetrahydrobenzo[d]thiazole Derivatives and their Anti- proliferative , c-Met Enzymatic Activity and Tyrosine Kinases Inhibitions

278 | Mar 25 2022

Rafat M Mohareb et al. found that anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions. [Read the Full Post]

Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases

256 | Mar 21 2022

Su'an Tang et al. provided a background on autoimmune diseases and provided an update on investigational SYK inhibitors. [Read the Full Post]

Insulin-like signaling promotes limb regeneration in the Chinese mitten crab (Eriocheir sinensis)

261 | Mar 20 2022

Ju Li et al. identified a conserved insulin-like receptor in E. sinensis, and provided new evidence for the involvement of ILS in the regulation of limb autotomy and regeneration in crustaceans. [Read the Full Post]

What's new in myeloproliferative neoplasia

640 | Mar 19 2022

Stefan Schmidt et al. revealed components of the alarmin complex (S100A8 und S100A9) drove this local sterile inflammation process, which also represented a potential therapeutic target, as the S100A8 and A9 inhibitor Tasquinimod reduced fibrosis in a pre-clinical animal model. [Read the Full Post]

Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture

700 | Mar 19 2022

M C B Lira-Nogueira et al. found that internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. [Read the Full Post]

The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia

557 | Mar 18 2022

Theodoros Karantanos et al. implicated CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. [Read the Full Post]

Ponatinib, Lestaurtinib, and mTOR/PI3K Inhibitors Are Promising Repurposing Candidates against Entamoeba histolytica

319 | Mar 17 2022

Monica M Kangussu-Marcolino et al. found that all 26 compounds were active against metronidazole-resistant E. histolytica, and 24 were able to block parasite recrudescence after drug removal. [Read the Full Post]

The effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

779 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

758 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner

328 | Mar 09 2022

Iris Eke et al. found that understanding the molecular short- and long-term changes after irradiation could aid in optimizing the efficacy of multimodal radiation oncology in combination with post-irradiation molecularly-targeted drug treatment and improving the outcome of prostate cancer patients. [Read the Full Post]

FGFR2 Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma

206 | Mar 09 2022

James M Cleary et al. revealed that these FGFR2 EIDs were sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic. [Read the Full Post]

A FAK Inhibitor Boosts Anti-PD1 Immunotherapy in a Hepatocellular Carcinoma Mouse Model

416 | Mar 05 2022

Yuhua Wei et al. suggested that combination of the FAK inhibitor VS4718 and anti-PD1 could be a potential therapy for HCC by improving the immune environment, reducing liver fibrosis and simultaneously preventing PD1 from binding to the increased PD-L1 induced by FAK inhibitor VS4718. [Read the Full Post]

The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM)

317 | Mar 04 2022

Man Lee Yuen et al. showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. [Read the Full Post]

Medical Therapy for Craniopharyngiomas

379 | Feb 24 2022

Krystallenia I Alexandraki et al. conducted a systematic review to identify case series or case reports with patients currently treated with systemic medical therapy. [Read the Full Post]

The role of fibroblast growth factor receptor (FGFR) protein-tyrosine kinase inhibitors in the treatment of cancers including those of the urinary bladder

208 | Feb 21 2022

Robert Roskoski Jr thought that the FDA approval of erdafitinib for the treatment of urinary bladder cancers might stimulate additional work targeting the many other FGFR-driven neoplasms. [Read the Full Post]

Pro-Inflammatory and Pro-Oxidative Changes During Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

483 | Feb 20 2022

Anna Sicuranza et al. showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib. [Read the Full Post]

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia

312 | Feb 19 2022

Miklos Egyed et al. showed a high rate of molecular remission without an impaired safety profile. Adverse events, with an occurrence rate of >20%, were as follows: grade 1-2 myelosuppression, gastrointestinal toxicity, rash, constitutional symptoms; grade 3 or 4 toxicities were syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia. [Read the Full Post]

Acalabrutinib CYP3A mediated Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to inform dose adjustment strategy

244 | Feb 18 2022

Buyun Chen et al. suggested that current PBPK model could be used to propose dose adjustment for drug interactions via CYP3A. [Read the Full Post]

ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation

174 | Feb 16 2022

Yan Gu et al. found that a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

0 | Feb 08 2022

C Dinkic et al. found that Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. [Read the Full Post]

The Relationship Between the Distribution of Training Intensity and Performance of Kayak and Canoe Sprinters: A Retrospective Observational Analysis of One Season of Competition

182 | Feb 07 2022

Manuel Matzka et al. showed that this seasonal analysis of the effects of training revealed extensive inter-individual variability. [Read the Full Post]

HER2 Tyrosine Kinase Inhibitors in the Sensitization to Cancers Resistant to HER2 Antibodies

411 | Jan 30 2022

Heena Singla et al. thought that act synergistically with the HER2-antibody resulting in an additive clinical response in patients. [Read the Full Post]

Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer

321 | Jan 30 2022

Louise C Brown et al. found that adaptive stratified medicine platform studies were feasible in common cancers but present challenges. [Read the Full Post]

Rifampin and ritonavir increase oral availability and elacridar enhances overall exposure and brain accumulation of the NTRK inhibitor larotrectinib

267 | Jan 26 2022

Yaogeng Wang et al.found that elacridar enhanced both larotrectinib plasma and tissue exposure and especially relative brain penetration, which might be therapeutically relevant. [Read the Full Post]

Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

390 | Jan 19 2022

Matthew Z Guo et al.discussed limitations of capmatinib, and highlighted ongoing trials of capmatinib in combinatorial approaches. [Read the Full Post]

Novel function of THEMIS2 in the enhancement of cancer stemness and chemoresistance by releasing PTP1B from MET

388 | Jan 18 2022

Wei-Chieh Huang et al. found that non-cytotoxic dosages of cryptotanshinone (CPT) could potently inhibit cancer stemness, chemoresistance and tumorigenicity by suppressing expression of THEMIS2. [Read the Full Post]

Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events

187 | Jan 10 2022

Hideki Imano et al. thought that activation of inflammasomes contributes to the idiosyncratic reactions associated with semaxanib and sorafenib. [Read the Full Post]

VEGFR 2 in vascular smooth muscle cells mediates H 2 S-induced dilation of the rat cerebral basilar artery

224 | Jan 10 2022

Jinhua Chen et al. found that H2S-induced CBA dilation and reduction of [Ca2+]i in VSMCs occured by acting on VEGFR2. [Read the Full Post]

The MSP-RON pathway regulates liver fibrosis through transforming growth factor beta-dependent epithelial-mesenchymal transition

292 | Jan 09 2022

Tianhao Weng et al. revealed that MSP was an important biomarker in liver cirrhosis progression and could be used to prognose patients. [Read the Full Post]

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

287 | Jan 07 2022

Hui-Jun Wang et al. found that Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib. [Read the Full Post]

Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors

304 | Jan 05 2022

Yilin Bao et al. found significant correlations of DNA methylation of specific CpG sites with response to the FGFR1/3-selective inhibitors PD 173074 and AZD4547, predominantly within the transcription start site of CCND1. [Read the Full Post]

Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue

391 | Jan 02 2022

Changxing Li et al. provided new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM. [Read the Full Post]

Safety of Anlotinib Capsules Combined with PD-1 Inhibitor Camrelizumab in the Third-Line Treatment of Advanced Non-Small-Cell Lung Cancer and Their Effect on Serum Tumor Markers

311 | Dec 30 2021

Yinhua Wang et al. found that application of anlotinib capsules combined with the PD-1 inhibitor (camrelizumab) in the third-line treatment of advanced NSCLC could effectively reduce the levels of serum tumor markers and cancer fatigue degree of patients. [Read the Full Post]

Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib

245 | Dec 30 2021

Fangling Hu et al. suggested that anlotinib could potentially treat HNSCC. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

0 | Dec 20 2021

Jiyeon Yun et al. suggested that YH25448 was a promising third-generation EGFR inhibitor, which might be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Cardiac Safety Assessment of Lazertinib: Findings From Patients With EGFR Mutation-Positive Advanced NSCLC and Preclinical Studies

491 | Dec 19 2021

Seong Bok Jang et al. indicated that lazertinib was not associated with increased cardiac risk. [Read the Full Post]

Drug repurposing for COVID-19 using computational screening: Is Fostamatinib/R406 a potential candidate?

550 | Dec 18 2021

Sovan Saha et al. found that Fostamatinib (R406 as its active promoiety) may also be considered as one of the potential candidates for further clinical trials in pursuit to counter the spread of COVID-19. [Read the Full Post]

Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia

0 | Dec 12 2021

Valentina Serafin et al. found that GC-sensitive cells cultured with IL-4 displayed an increased resistance to dexamethasone, whereas the inhibition of IL-4 signaling could increase GC-induced apoptosis in resistant cells. [Read the Full Post]

Detection of gene mutations and gene-gene fusions in circulating cell-free DNA of glioblastoma patients: an avenue for clinically relevant diagnostic analysis

563 | Dec 11 2021

Vikrant Palande et al. found that new avenues for precision medicine in GBM, using non-invasive liquid biopsy diagnostics to assess personalized patient profiles. Moreover, repeated detection of druggable targets over the course of the disease may provide real-time information on the evolving molecular landscape of the tumour. [Read the Full Post]

Detection of gene mutations and gene-gene fusions in circulating cell-free DNA of glioblastoma patients: an avenue for clinically relevant diagnostic analysis

526 | Dec 10 2021

Vikrant Palande et al. suggested that integrated analysis of cfDNA plasma concentration, gene mutations and gene-gene fusions could serve as a diagnostic modality for distinguishing GBM patients who might benefit from targeted therapy. [Read the Full Post]

Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial

569 | Dec 02 2021

Xiuning Le et al. found that Poziotinib demonstrated antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC. [Read the Full Post]

Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer

573 | Dec 02 2021

J Robert McCorkle et al. thought that lapatinib and poziotinib combined with paclitaxel synergizes to inhibit the proliferation of ABCB1-overexpressing ovarian cancer cells in vitro. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Dec 01 2021

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

924 | Nov 30 2021

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseases mediated by osteoclasts. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

0 | Nov 26 2021

Cristina Zahonero et al. found that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status. [Read the Full Post]

MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms

841 | Nov 25 2021

Timothy D Calamaras et al. suggested augmenting MLK3 kinase activity could preserve LV function in HF but avoid hypotension from PKG1α activation. [Read the Full Post]

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

0 | Nov 24 2021

Maria Kost-Alimova et al. suggested fostamatinib as a repurposing drug candidate for ALI. [Read the Full Post]

Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations

820 | Nov 14 2021

Brion W Murray et al. thought that repotrectinib was the most potent inhibitor of wild-type TRKA/B/C fusions and was more potent than selitrectinib against all tested resistance mutations. [Read the Full Post]

Translational Strategies for Repotrectinib in Neuroblastoma

711 | Nov 14 2021

Tara J O'Donohue et al. demonstrated that repotrectinib had antitumor activity in genotypically diverse neuroblastoma models. [Read the Full Post]

Construction of a ceRNA Network and Analysis of Tumor Immune Infiltration in Pancreatic Adenocarcinoma

511 | Nov 12 2021

Jingjing Xiao et sl. suggested that the IC50 values of gemcitabine in PAAD were not significantly different between the high and low risk groups. [Read the Full Post]

Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer

239 | Nov 10 2021

Leylah M Drusbosky et al. found that TKIs could cross the blood brain barrier and demonstrated some activity toward CNS metastases. [Read the Full Post]

ROS generation is involved in titanium dioxide nanoparticle-induced AP-1 activation through p38 MAPK and ERK pathways in JB6 cells

468 | Nov 04 2021

Lu Kong et al. found that ROS generation was involved in TiO2 NPs-induced AP-1 activation mediated by MAPKs signal pathway. [Read the Full Post]

ALK Rearrangement in Small-Cell Lung Cancer and Durable Response to Alectinib: A Case Report

357 | Nov 04 2021

Ning Sun et al. found that the allele frequency of ALK rearrangement and RB1 and TP53 mutations in plasma circulating tumor DNA decreased with the reduction in tumor size. [Read the Full Post]

FAK-targeting PROTAC demonstrates enhanced antitumor activity against KRAS mutant non-small cell lung cancer

535 | Nov 03 2021

Jinyuan Liu et al. thought that PROTACs might serve as promising therapeutic agents for the intractable NSCLC harboring KRAS mutations. [Read the Full Post]

Crosstalk between Cancer Cells and Fibroblasts for the Production of Monocyte Chemoattractant Protein-1 in the Murine 4T1 Breast Cancer

493 | Nov 01 2021

Mayu Imamura et al. thought that although cancer cells had the capacity to crosstalk with fibroblasts via PDGFs, this crosstalk did not play a major role in MCP-1 production or cancer progression in this model. [Read the Full Post]

ZCCHC14 regulates proliferation and invasion of non-small cell lung cancer through the MAPK-P38 signalling pathway

823 | Oct 25 2021

Xiuying Shi et al. found that ZCCHC14 could regulate proliferation and invasion of NSCLC through the P38 pathway. [Read the Full Post]

Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages

900 | Oct 24 2021

Robin C Su et al. discovered that through a high-throughput, unbiased kinase activity profiling strategy, MC-LR-induced phosphorylation events were compared with potential inhibitors, and doramapimod was found to effectively prevent MC-LR-induced inflammatory responses in macrophages. [Read the Full Post]

Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

263 | Oct 18 2021

Gaëtan Poulen et al. found that a transient oral GW2580 treatment post-injury might provide a promising therapeutic strategy for SCI patients and might also be extended to other central nervous system disorders displaying microglia activation. [Read the Full Post]

FMS-Like Tyrosine Kinase 3 Inhibitors for the Treatment of Acute Myeloid Leukemia

480 | Oct 16 2021

Elli D Novatcheva found that the clinical trials/evidence, similarities, differences, clinical toxicities, and drug interactions relevant to treating clinicians as pertains to 5 FLT3-inhibitors: midostaurin, sorafenib, gilteritinib, crenolanib, and quizartinib. [Read the Full Post]

Modelling hypersensitivity to trastuzumab defines biomarkers of response in HER2 positive breast cancer

693 | Oct 15 2021

Laura Díaz-Gil et al. thought that the identification of trastuzumab response biomarkers might be used to select patients particularly sensitive to facilitate the use of trastuzumab-based therapies and refine follow-up guidelines in patients with HER2+ tumors. [Read the Full Post]

HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells

1065 | Oct 14 2021

Petros X E Mouratidis et al. found that sub-ablative heating could act synergistically with the clinically relevant HSP90 inhibitor NVP-AUY922 to induce a pro-immunogenic form of cell death in colon cancer cells. [Read the Full Post]

Evolution of kinase polypharmacology across HSP90 drug discovery

1051 | Oct 13 2021

Albert A Antolin et al. found that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, displayed unique off-target kinase pharmacology as compared with other HSP90 inhibitors. [Read the Full Post]

Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents

803 | Oct 12 2021

Hanyi Tan et al. suggested that 16c inhibited the malignant proliferation of hepatocellular carcinoma (HCC) cells through decreasing the phosphorylation in the FAK cascade. [Read the Full Post]

Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis

1037 | Oct 06 2021

Maria Niccum et al. found that potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology. [Read the Full Post]

Nintedanib Regulates GRK2 and CXCR2 to Reduce Neutrophil Recruitment in Endotoxin-Induced Lung Injury

660 | Oct 02 2021

Vincent Yi-Fong Su et al. found that the inhibition of adhesion molecules via the activation of GRK2 and the inhibition of p38 MAPK and CXCR2. [Read the Full Post]

Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

395 | Sep 26 2021

Nicole J Chew et al. found the potential of specific FGFRs, including FGFR4, as targets for precision treatment. [Read the Full Post]

Machine learning identifies molecular regulators and therapeutics for targeting SARS-CoV2-induced cytokine release

615 | Sep 22 2021

Marina Chan et al. proposed that agented targeting multiple kinases required for SARS-CoV-2-mediated cytokine release, such as ponatinib, might represent an attractive therapeutic option for treating moderate to severe COVID-19. [Read the Full Post]

EGFR and ERK activation resists flavonoid quercetin-induced anticancer activities in human cervical cancer cells in vitro

604 | Sep 21 2021

Xin Chen et al.determined the role of EGFR and the underlying signaling pathways involved in the anti-cervical cancer malignant behavior induced by Que and identified the negative regulatory association. [Read the Full Post]

Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

567 | Sep 20 2021

Fabio Forghieri et al. thought that future studies were warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies might have potential clinical utility in NPM1-mutated AML patients. [Read the Full Post]

The Combined Treatment With the FLT3-Inhibitor AC220 and the Complex I Inhibitor IACS-010759 Synergistically Depletes Wt- and FLT3-Mutated Acute Myeloid Leukemia Cells

515 | Sep 20 2021

Xiyuan Lu et al. identified a novel drug combination, AC220 and IACS-010759. [Read the Full Post]

An organ-on-a-chip model for pre-clinical drug evaluation in progressive non-genetic cardiomyopathy

741 | Sep 19 2021

Erika Yan Wang et al. found multifaceted cardioprotective effects of relaxin in restoring contractile function and reducing fibrotic remodeling. [Read the Full Post]

Effects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial

636 | Sep 17 2021

Krishna T Patel et al. suggested a possible therapeutic role for Src/Fyn kinase inhibitors in AUD risk. [Read the Full Post]

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK

779 | Sep 07 2021

Long-Sheng Chang et al. demonstrated the power of the de novo unbiased approach for drug discovery and represented a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies. [Read the Full Post]

Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases Wachiraphan Supsavhad 1 2, Bardes B Hassan 1 3,

1510 | Sep 05 2021

Wachiraphan Supsavhad et al. showed that SP600125 had the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression. [Read the Full Post]

Immunotherapy in Hepatocellular Carcinoma

1115 | Aug 27 2021

Claudia A M Fulgenzi et al. thought that in the absence of predictive biomarkers, choice of immunotherapy over kinase inhibitors would continue to remain an empirical exercise, guided by balancing anti-tumour efficacy with toxicity considerations in the individual patient. [Read the Full Post]

Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study

400 | Aug 26 2021

Milind Javle et al. found that infigratinib had promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements. [Read the Full Post]

Targeted inhibition of FGF19/FGFR cascade improves antitumor immunity and response rate in hepatocellular carcinoma

376 | Aug 26 2021

David Wai Meng Tai et al. suggested that HCC patients with high FGFR2/3 or FGF19/FGFR4 expressing tumors might benefit from a combination infigratinib/FGF401. [Read the Full Post]

Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma

915 | Aug 25 2021

Sarah Waliany et al. thought that monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib. [Read the Full Post]

IL-1β-induced Elevation of SLC7A11 Promotes Hepatocellular Carcinoma Metastasis through Upregulating PD-L1 and CSF1

332 | Aug 19 2021

Qin He et al. found that IL-1β-induced SLC7A11 overexpression upregulated PD-L1 and CSF1 through αKG/HIF1α axis, which promoted TAMs and MDSCs infiltration. [Read the Full Post]

MiR-221 confers lapatinib resistance by negatively regulating p27 kip1 in HER2-positive breast cancer

926 | Aug 16 2021

Thanh Kieu Huynh et al. suggested Src inhibition as a potential strategy to overcome lapatinib resistance. [Read the Full Post]

Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer

306 | Aug 13 2021

Stefan Prekovic et al. showed that GR activation induced reversible cancer cell dormancy characterised by anticancer drug tolerance, and activation of growth factor survival signalling accompanied by vulnerability to inhibitors. [Read the Full Post]

A systems-level study reveals host-targeted repurposable drugs against SARS-CoV-2 infection

291 | Aug 12 2021

Fangyuan Chen et al. found that almeterol, rottlerin, and mTOR inhibitors exhibited antiviral activities in Vero-E6 cells; imipramine, linsitinib, hexylresorcinol, ezetimibe, and brompheniramine impaired viral entry. [Read the Full Post]

Inhibition of AKR1B10-mediated metabolism of daunorubicin as a novel off-target effect for the Bcr-Abl tyrosine kinase inhibitor dasatinib

1242 | Aug 09 2021

Neslihan Büküm et al. demonstrated that dasatinib could synergize with Daun in human cancer cells and enhance its therapeutic effectiveness. [Read the Full Post]

Predictors of Response and Survival to Multikinase Inhibitors in Radioiodine Resistant Differentiated Thyroid Cancer

918 | Aug 08 2021

Tiziana Feola et al. provided an overview of the predictive factors for the response and survival of sorafenib and lenvatinib in RR-DTC. [Read the Full Post]

Bruton's tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma

675 | Aug 01 2021

Chi-Tai Yeh et al. suggested that BTK mediated stemness and EMT properties, and inhibition of BTK potentiated the effect of Gefitinib and Osimertinib in NSCLC cells resistant to TKI. [Read the Full Post]

Identification of DNA-Repair-Related Five-Gene Signature to Predict Prognosis in Patients with Esophageal Cancer

557 | Jul 30 2021

Lin Wang et al. found that small-molecule drugs (trametinib, selumetinib, and refametinib) could help to improve patient survival. [Read the Full Post]

The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis

450 | Jul 30 2021

Dennis Kobelt et al. found that MAP kinase signaling was not linear leading to ERK activation, but branched at the level of MEK1. [Read the Full Post]

Cordycepin inhibits inflammatory responses through suppression of ERK activation in zebrafish

434 | Jul 25 2021

Wei Liu et al. found that the important roles of cordycepin in inhibiting LPS and injury-induced inflammation. [Read the Full Post]

XHL11, a novel selective EGFR inhibitor, overcomes EGFR T790M-mediated resistance in non-small cell lung cancer

500 | Jul 07 2021

Yi Li et al. thought that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients. [Read the Full Post]

Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600 mut melanoma patients

594 | Jul 02 2021

M Raynal et al. thought that monitoring PCD and PCT alone was unlikely to be useful in assessing response to treatment. [Read the Full Post]

AXL receptor tyrosine kinase: a possible therapeutic target in acute promyelocytic leukemia

306 | Jul 01 2021

Mariam Fatima et al. suggested targeting of AXL-RTK in the treatment of therapy resistant APL patients. [Read the Full Post]

Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome

261 | Jul 01 2021

Albert Morales et al. thought that plasma GAS6 and AXL levels reflected COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19. [Read the Full Post]

Suppression of Microgliosis With the Colony-Stimulating Factor 1 Receptor Inhibitor PLX3397 Does Not Attenuate Memory Defects During Epileptogenesis in the Rat

550 | Jun 29 2021

Season K Wyatt-Johnson eal. revealed that PLX3397 did not improve or worsen the memory deficits in rats that sustained pilocarpine-induced SE. [Read the Full Post]

Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia

595 | Jun 28 2021

Catherine C Smith et al. thought that Mutations in CCND3, a gene not commonly mutated in AML, were a novel cause of clinical primary resistance to FLT3 inhibitors in AML and might have sensitivity to CDK4/6 inhibition. [Read the Full Post]

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

1188 | Jun 27 2021

Joshua N Gustine et al. revealed that continuation of ibrutinib until subsequent treatment was associated with improved disease control and clinical outcomes. [Read the Full Post]

Genetic variant within CDK6 regulates immune response to palbociclib treatment

592 | Jun 17 2021

Valentina Serra et al. suggested that the effect of palbociclib treatment might depend on underlying genetically encoded individual immune response as well as the direct response to the drug. [Read the Full Post]

Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase-positive non-small cell lung cancer with triple problems: carcinomatous meningitis, poor performance status, and dysphagia-a case report

533 | Jun 16 2021

Kota Sasaki et al. thought that lorlatinib could be a treatment option for patients with ALK-positive NSCLC showing carcinomatous meningitis, poor PS, and dysphagia upon failure of other ALK inhibitor-based treatments. [Read the Full Post]

Impact of tumor growth rate during preceding treatment on tumor response to nivolumab or irinotecan in advanced gastric cancer

619 | Jun 15 2021

K Kato et al. suggested that NIVO treatment was a more favorable option for patients with slow-growing tumors, and NIVO and IRI were similarly recommended for patients with rapid-growing tumors in refractory AGC. TGR and NL emergence during preceding treatment might be helpful for drug selection and warrant further investigation. [Read the Full Post]

YAP/TAZ suppress drug penetration into hepatocellular carcinoma via stromal activation

1014 | Jun 15 2021

Kyungjoo Cho et al. indicated that drug delivery into liver cancer was impaired by YAP/TAZ signaling in tumor cells and subsequent activation of stroma by the signaling. [Read the Full Post]

Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study

532 | Jun 14 2021

Vivek Subbiah et al. found that Pralsetinib was a new, well-tolerated, potent once-daily oral treatment option for patients with RET-altered thyroid cancer. [Read the Full Post]

Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study

417 | Jun 13 2021

Katharina C Kähler et al. found that favorable therapy outcome upon vemurafenib plus cobimetinib. [Read the Full Post]

Soyasaponin A 2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline Deficient (MCD) Diet-induced Non-alcoholic Steatohepatitis (NASH) Mice

389 | Jun 09 2021

Fei Xiong et al. found that SS-A2 alleviated steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice. [Read the Full Post]

Triazole antifungal use for prophylaxis and treatment of invasive fungal diseases for patients receiving gilteritinib

703 | Jun 08 2021

Muneerah M Aleissa et al. found that concomitant gilteritinib and triazole therapy was feasible and was not associated with clinically meaningful increase in gilteritinib-related AEs. [Read the Full Post]

Analysis of chemotherapy-induced peripheral neuropathy using the Japanese Adverse Drug Event Report database

734 | Jun 02 2021

Misaki Inoue et al. revealed several drugs associated with a high risk for CIPN development. [Read the Full Post]

Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression

871 | May 30 2021

Kun Liu et al. demonstrated that ivacaftor decreased stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. [Read the Full Post]

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China

1011 | May 28 2021

Jing Ni et al. found that it was feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population could acquire promising efficacy and tolerance. [Read the Full Post]

IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK

457 | May 26 2021

Christine E Lehman et al. found that treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. [Read the Full Post]

ALK-negative lung inflammatory myofibroblastic tumor in a young adult: A case report and literature review of molecular alterations

809 | May 24 2021

Silvia Angela Debonis et al. thought that although there was no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. [Read the Full Post]

Exosomes derived from miR-16-5p-overexpressing keratinocytes attenuates bleomycin-induced skin fibrosis

659 | May 24 2021

Yunyao Bo et al. thought that the localized delivery of miR-16-5p by keratinocytes-derived exosomes might have potential for efficient clinical treatment of skin fibrosis. [Read the Full Post]

Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy

572 | May 17 2021

Matthew J McConnell et al. thought that COVID-19 was associated with coagulopathy and endotheliopathy in the liver endothelium driven by IL-6 trans-signaling, a possible mechanism of liver injury. [Read the Full Post]

Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer

507 | May 14 2021

Muriel Lainé et al. reported for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. [Read the Full Post]

Novel human-derived RET fusion NSCLC cell lines have heterogeneous responses to RET inhibitors and differential regulation of downstream signaling

429 | May 09 2021

Laura Schubert et al. demonstrated that the RET inhibitor BLU-667 was effective at inhibiting tumor growth in CUTO42 tumors, but had a much less profound effect in CUTO32 tumors, consistent with in vitro experiments. [Read the Full Post]

IL33 (Interleukin 33)/ST2 (Interleukin 1 Receptor-Like 1) Axis Drives Protective Microglial Responses and Promotes White Matter Integrity After Stroke

260 | May 03 2021

Di Xie et al. found that the IL33/ST2/STAT6 signaling as a potential immune regulatory mechanism to modulate microglia/macrophage activity, improved white matter integrity, and restored long-term neurological functions after stroke. [Read the Full Post]

Ibrutinib combinations in CLL therapy: scientific rationale and clinical results

518 | May 01 2021

Natalia Timofeeva et al. found a new standard of care for CLL is expected to emerge from these investigations. [Read the Full Post]

Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease

417 | Apr 30 2021

Philipp von Hundelshausen et al. thought that specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi. [Read the Full Post]

Paeoniflorin exerts antidepressant-like effects through enhancing neuronal FGF-2 by microglial inactivation

593 | Apr 23 2021

Jie Cheng et al. found that paeoniflorin exhibited neuroprotective and antidepressant effects in mice, which might be mediated by activating neuronal FGF-2/FGFR1 signaling via the inhibition of microglial activation in the hippocampus. [Read the Full Post]

Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro

562 | Apr 20 2021

Menghuan Guo et al. suggested that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. [Read the Full Post]

Optimal Therapies for Recurrent Glioblastoma: A Bayesian Network Meta-Analysis

540 | Apr 20 2021

Wenlin Chen et al. indicated that bevacizumab (BEV) plus CCNU and regorafenib had a higher efficacy on the ORR, 6-m PFS rate and OS, and that BEV monotherapy or BEV combined with active drug therapies was advantageous for the ORR and 6-m PFS rate. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

1142 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

1548 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition

430 | Apr 13 2021

Narges K Gortany et al.indicated that foretinib might have the therapeutic potential against human GBM which deserve further investigation. [Read the Full Post]

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function

493 | Apr 09 2021

Tony J Zheng et al. found that TKIs targeting Syk or BTK inhibited central platelet functional responses but might differentially affect protein activities and organization in critical systems downstream of Syk and BTK in platelets. [Read the Full Post]

Pan- and Isoform-specific Inhibition of the Bromodomain and Extra-terminal Proteins and Evaluation of Synergistic Potential With Entospletinib in Canine Lymphoma

0 | Apr 09 2021

Weibo Kong et al. found that Entospletinib did not enhance the inhibitory effects of the pan- or isoform-specific BET. [Read the Full Post]

IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas

455 | Apr 07 2021

Qing Wang et al. found that the treatment of colon tumor cells with IGF-1R inhibitors stimulated p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics. [Read the Full Post]

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

1147 | Apr 06 2021

Irene Castellano-Pellicena et al. explored the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. [Read the Full Post]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

928 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

1023 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma

481 | Apr 02 2021

Robert Hanes et al. supported LY2874455 as a better therapy than NVP-BGJ398 for FRS2-amplified liposarcoma, and a clinical trial was warranted. [Read the Full Post]

Cardiomyocyte protective effects of thyroid hormone during hypoxia/reoxygenation injury through activating of IGF-1-mediated PI3K/Akt signalling

254 | Mar 31 2021

Bin Zeng et al. showed that T3 pretreatment protected cardiomyocytes against H/R-induced injury by activating the IGF-1-mediated PI3K/Akt signalling pathway. [Read the Full Post]

A Three-Dimensional Organoid Culture Model to Assess the Influence of Chemicals on Morphogenetic Fusion

311 | Mar 22 2021

David G Belair et al. demonstrated the utility of the in vitro fusion assay for identifying chemicals that disrupted human organoid morphogenesis in a scalable format amenable to toxicology screening. [Read the Full Post]

TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma

432 | Mar 22 2021

Lipika Goyal et al. demonstrated that the irreversible FGFR inhibitor TAS-120 provided clinical benefit in patients with resistance to BGJ398 or Debio 1347 and overcomed several FGFR2 mutations in ICC models. [Read the Full Post]

Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer

654 | Mar 21 2021

Yi Li et al. supported the notion that the radiosensitivity of radiation-resistant colorectal cancer cells could be enhanced by directly targeting IGF1R expression or activity. [Read the Full Post]

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

364 | Mar 19 2021

Xiaofeng Wan et al. thought that activation of the AKT1-CREB-PDGFRα signaling pathway contributed to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment. [Read the Full Post]

Cardioautonomic control in healthy singleton and twin pregnancies

667 | Mar 16 2021

Victoria L Meah wt al. suggested that individuals with twin pregnancies had greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control was impacted during twin compared to singleton pregnancy. [Read the Full Post]

Differential Outcomes in Codon 12/13 and Codon 61 NRAS-Mutated Cancers in the Phase 2 NCI-MATCH Trial of Binimetinib in Patients with NRAS-Mutated Tumors

566 | Mar 07 2021

James M Cleary et al. thought that the observation of increased OS and PFS in codon 61 NRAS-mutated colorectal cancer patients merited further investigation. [Read the Full Post]

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma

355 | Mar 03 2021

M -L Nairismägi found that the activity of PRN371 had a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. [Read the Full Post]

BTK gatekeeper residue variation combined with cysteine 481 substitution causes super-resistance to irreversible inhibitors acalabrutinib, ibrutinib and zanubrutinib

405 | Mar 01 2021

H Yesid Estupiñán et al. found that reversible inhibitors showed a variable pattern, from resistance to no resistance, collectively demonstrating the structural constraints for different classes of inhibitors, which might affect their clinical application. [Read the Full Post]

The role of acalabrutinib in adults with chronic lymphocytic leukemia

439 | Feb 28 2021

Bita Fakhri et al. demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

609 | Feb 19 2021

C Dinkic et al. thought that Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. was a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. [Read the Full Post]

Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells

318 | Feb 18 2021

Ji-Yeon Park et al. showed that Ripk2 signaling appeared to contribute to the F. nucleatum-induced immune response and could be a preventive and therapeutic target against APOs. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

585 | Feb 06 2021

Sean P Korpela 1 et al. found eterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells

492 | Feb 05 2021

Dae Woo Lee et al. found that the addition of tipifarnib or rottlerin to inhibit N‑Ras or p‑PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI‑6 in HeyA8 cells. [Read the Full Post]

Trichlorocarban induces developmental and immune toxicity to zebrafish (Danio rerio) by targeting TLR4/MyD88/NF-κB signaling pathway

673 | Feb 04 2021

Jiaqi Xu et al. found the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish. [Read the Full Post]

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

486 | Feb 01 2021

D Gwyn Bebb et al. recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options. [Read the Full Post]

Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro

679 | Jan 27 2021

Natalia Kosyakova et al. described the differential effects that two widely used stromal cell populations, fibroblasts (FBs) and pericytes (PCs), had on μVN formation. [Read the Full Post]

Suppression of MET signaling mediated by pitavastatin and capmatinib inhibits oral and esophageal cancer cell growth

738 | Jan 26 2021

Bo Xu et al. suggested that the combination of pitavastatin with capmatinib was a useful therapeutic strategy in OSCC and ESCC. [Read the Full Post]

Altered TGFβ/SMAD Signaling in Human and Rat Models of Pulmonary Hypertension: An Old Target Needs Attention

299 | Jan 20 2021

Takayuki Jujo Sanada et al. demonstrated considerable discrepancies in TGFβ-SMAD signaling between iPAH and hPAH patients, as well as between patients and rats with experimental PAH. [Read the Full Post]

Pathological significance of abnormal recepteur d'origine nantais and programmed death ligand 1 expression in colorectal cancer

404 | Jan 19 2021

Yi-Zhi Liu et al. found that RON, PD-L1, and their crosstalk were significant in predicting the prognostic value of CRC. [Read the Full Post]

Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events

269 | Jan 19 2021

Hideki Imano et al. found that activation of inflammasomes contributed to the idiosyncratic reactions associated with semaxanib and sorafenib. [Read the Full Post]

Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

318 | Jan 16 2021

Christos Vallilas et al. found that alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors). [Read the Full Post]

Kanglexin accelerates diabetic wound healing by promoting angiogenesis via FGFR1/ERK signaling

428 | Jan 15 2021

Yixiu Zhao et al. thought that KLX had the potential to be developed as a topical drug to promote diabetic wound healing. [Read the Full Post]

CB 1 Cannabinoid Receptors Stimulate Gβγ-GRK2-Mediated FAK Phosphorylation at Tyrosine 925 to Regulate ERK Activation Involving Neuronal Focal Adhesions

647 | Jan 12 2021

George D Dalton et al. found that FAK 925 Tyr-P occured concurrently with CB1-stimulated ERK2 activation and required the actin cytoskeleton and Gi/oβγ-GRK2-mediated cross-talk between CB1, integrins, and receptor tyrosine kinases (RTKs). [Read the Full Post]

Mechanotransduction-targeting Drugs Attenuate Stiffness-induced Hepatic Stellate Cell Activation in vitro

608 | Jan 10 2021

Mutsuko Sakai et al. showed that an integrin antagonist and mechanotransduction-targeting drugs reduced stiffness-induced HSC activation in a dose-dependent fashion. [Read the Full Post]

Anlotinib enhances the antitumor activity of radiofrequency ablation on lung squamous cell carcinoma

297 | Jan 08 2021

Wei Zhou et al. proposed a combinative strategy of RFA and anlotinib as a novel approach for successful management of LSCC. [Read the Full Post]

Anlotinib Plus S-1 for Patients with EGFR Mutation-Negative Advanced Squamous Cell Lung Cancer with PS Scores of 2-3 After Progression of Second-Line or Later-Line Treatment

288 | Jan 08 2021

Xiao-Hong Xie et al. thought that advanced SqCLC patients with higher PS scores still benefited from anlotinib and S-1 combination regimen, even after they failed second-line or later-line systemic treatment. [Read the Full Post]

EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation

448 | Dec 30 2020

Sehhoon Park et al. reported the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. [Read the Full Post]

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

529 | Dec 29 2020

Maria Kost-Alimova et al. suggested fostamatinib as a repurposing drug candidate for ALI. [Read the Full Post]

Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer

757 | Dec 23 2020

Hedvig Elfving et al. found that the presence of NTRK fusion genes in non-small cell lung cancer was exceedingly rare. The use of the immunohistochemical NTRK assay would result in a small number of false positive cases. [Read the Full Post]

Clinicopathologic, Genomic, and Protein Expression Characterization of 356 ROS1 Fusion Driven Solid Tumors Cases

700 | Dec 22 2020

Richard S P Huang et al. characterized a large cohort of ROS1 fusionpos NSCLC and non-NSCLC solid tumors and discovered 10 novel ROS1 fusions. [Read the Full Post]

Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway

623 | Dec 15 2020

Heejin Lee et al. suggested that HER4 might be a promising therapeutic target for ovarian CSCs, and that poziotinib might be an effective therapeutic option for the prevention of ovarian cancer recurrence. [Read the Full Post]

Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells

531 | Dec 14 2020

Yongchao Zhang et al. showed that poziotinib interacted with the ABCB1 and ABCG2 transporter, suggesting that poziotinib might increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

1558 | Dec 13 2020

Ryo Kanamoto et al. demonstrated an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

0 | Dec 12 2020

Alejandro Torres-Hernandez et al. found that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

814 | Dec 08 2020

Cristina Zahonero et al. confirmd that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it was less effective in a PTEN-deleted GBM line). [Read the Full Post]

Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity

1023 | Dec 07 2020

Sandeep Kumar et al. demonstrated that MLK3 played an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer. [Read the Full Post]

A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic

379 | Dec 06 2020

Maria Alimova et al. revealed Fostamatinib as a repurposing drug candidate for ALI and provided the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury. [Read the Full Post]

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

0 | Nov 24 2020

Diana Cervantes-Madrid et al. showed that repotrectinib was capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibited strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Cases of ROS1-rearranged lung cancer: when to use crizotinib, entrectinib, lorlatinib, and beyond?

685 | Nov 23 2020

Kartik Sehgal et al. described cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients. [Read the Full Post]

Cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases: an overview of systematic reviews

454 | Nov 21 2020

Vakaramoko Diaby et al. examined evidence on the cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases through a review of systematic reviews on the topic. [Read the Full Post]

The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary Renal Cell Carcinoma Patient-Derived Xenograft Models

278 | Nov 19 2020

Alwin G Schuller et al. provided the first report testing therapeutics in preclinical in vivo models of PRCC and supported the clinical development of AZD6094 in the indication. [Read the Full Post]

Alectinib-Associated Perforated Duodenal Ulcer

416 | Nov 14 2020

Maximilian J Hochmair et al. found that later-line lorlatinib treatment could induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer. [Read the Full Post]

Defactinib attenuates osteoarthritis by inhibiting positive feedback loop between H-type vessels and MSCs in subchondral bone

599 | Nov 13 2020

Yanjun Hu et al. demonstrated that defactinib inhibited OA by suppressing the positive feedback loop between H-type vessels and MSCs in subchondral bone. [Read the Full Post]

Dexmedetomidine reduces ventilator-induced lung injury via ERK1/2 pathway activation

562 | Nov 13 2020

Chun-Hua Zhu et al. found that dexmedetomidine reduced the inflammatory response and epithelial cell death caused by VILI, via the activation of the ERK1/2 signaling pathway. [Read the Full Post]

Wu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways

482 | Nov 10 2020

Miao Yu et al. demonstrated that Wu-5, a novel USP10 inhibitor, could overcome FLT3 inhibitor resistance and synergistically enhance the anti-AML effect of crenolanib through targeting FLT3 and AMPKα pathway. [Read the Full Post]

Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy

318 | Oct 23 2020

S Furquan Ahmad et al.suggested that CSF-1 was involved in the survival and proliferation of trophoblast cells in EP and pharmacological disruption of CSF-1/CSF-1R signaling axis could be the basis of a new therapeutic for EP. [Read the Full Post]

FLT3 inhibitors in the treatment of Acute Myeloid Leukemia: current status and future perspectives

405 | Oct 20 2020

Adrián Mosquera Orgueira et al.focused on the role of FLT3 mutations in AML, pharmacological features of FLT3 inhibitors, known mechanisms of drug resistance and accumulated evidence for the use of FLT3 inhibitors in different clinical settings. [Read the Full Post]

SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

566 | Oct 19 2020

Hao Chen et al.found that SHP2 constituted a shared signaling node allowing MBC cells to simultaneously engage a diversity of growth and survival pathways, including those derived from the ECM. [Read the Full Post]

Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line

812 | Oct 16 2020

Mahshid Mohammadian et al. indicated an effective action of NVP-AUY922 in combined with DOX in this cell line. [Read the Full Post]

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

852 | Oct 15 2020

Ankit K Rochani et al.suggested that DNP-based aqueous nanoformulations could be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy. [Read the Full Post]

An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications

686 | Oct 14 2020

Yihui Shi et al.supported the broad potential for the development of agents that targeted the spliceosome for the treatment of cancer and other diseases, as well as new avenues for the discovery of new chemotherapeutic agents for a range of diseases. [Read the Full Post]

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report

888 | Oct 03 2020

Naoko Tanaka et al. believed that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine. [Read the Full Post]

Advances on Synthesis, Derivatization and Bioactivity of Isatin: A Review

360 | Sep 28 2020

Garima Chauhan et al. reviewed the different strategies for the designs and synthesis of several IST based compounds having different biological activities with SAR which could favour further investigation and modification for the development of new and more potent entities. [Read the Full Post]

FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential

328 | Sep 19 2020

Jinglin Zhang et al. highlighted the translational potential of FGFR2-c-Jun-YAP1 axis, which might serve as a prognostic biomarker and therapeutic target for GC. [Read the Full Post]

Flavonoids Restore Platinum Drug Sensitivity to Ovarian Carcinoma Cells in a Phospho-ERK1/2-Dependent Fashion

467 | Sep 15 2020

Yifat Koren Carmi et al. showed the potential of combining flavonoids with standard therapy to restore drug sensitivity to OC cells and overcomed TME-mediated platinum drug resistance. [Read the Full Post]

FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia

551 | Sep 14 2020

Jun Long et al. demonstrated that HDAC8 upregulation was an important mechanism to resist TKIs and promote leukemia maintenance and suggested that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation-harboring leukemias. [Read the Full Post]

Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation

591 | Sep 14 2020

Julian Shen et al. provided the multitarget mechanisms for application of AD in the treatment of atherosclerosis. [Read the Full Post]

Structural Basis of Activin Receptor-Like Kinase 2 (R206H) Inhibition by Bis-heteroaryl Pyrazole-Based Inhibitors for the Treatment of Fibrodysplasia Ossificans Progressiva Identified by the Integration of Ligand-Based and Structure-Based Drug Design Approaches

470 | Sep 13 2020

Tomohiro Sato et al. indicated the existence of the additional hydrogen bond via water molecules restricting the attachment point in the pyrazole scaffold [Read the Full Post]

Quizartinib for the treatment of acute myeloid leukemia

557 | Sep 13 2020

Alejandro Garcia-Horton et al. reviewed the mechanism of action, pharmacology, clinical efficacy, and safety of quizartinib, a FLT3 inhibitor, for the treatment of acute myeloid leukemia. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

0 | Sep 11 2020

Vanita Noronha et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Anti-inflammatory Effect of AZD6244 on Acrolein-Induced Neuroinflammation

491 | Sep 10 2020

Wen-Chien Ho et al. suggested that ERK inhibition may be a neuroprotective target against acrolein-induced neuroinflammation in the CNS neurodegenerative diseases. [Read the Full Post]

Dual inhibition of Src and PLK1 regulate stemness and induce apoptosis through Notch1-SOX2 signaling in EGFRvIII positive glioma stem cells (GSCs)

631 | Sep 09 2020

Xuetao Li et al. indicated that p-Src and PLK1 contributed to cancer stemness in EGFRvIII-positive GSCs by driving Notch1-SOX2 signaling, a finding that had important clinical implications. [Read the Full Post]

IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer

646 | Sep 09 2020

Nadine Bley et al. provided a rationale for the therapeutic benefit of combinatorial SRC/MEK inhibition in mesenchymal-like HGSOC. [Read the Full Post]

Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

528 | Aug 23 2020

Abhay Singh et al. provided a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlighted current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

1318 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience

455 | Aug 09 2020

Vera Espírito Santo et al. showed that the drug was associated with clinical and radiological improvement. [Read the Full Post]

Regorafenib for Metastatic Colorectal Cancer: An Analysis of a Registry-Based Cohort of 555 Patients

846 | Aug 06 2020

Alena Novakova-Jiresova ETAL. found that regorafenib was a safe and active treatment option for a subgroup of patients with mCRC who were progressing after other systemic therapies and maintain good performance status. [Read the Full Post]

Inhibition of FGF2-Mediated Signaling in GIST-Promising Approach for Overcoming Resistance to Imatinib

374 | Aug 05 2020

Sergei Boichuk et al. provided a rationale to evaluate the effectiveness of the inhibitors of FGF-signaling for IM-resistant GISTs. [Read the Full Post]

Inhibition of FGFR Signaling Partially Rescues Osteoarthritis in Mice Overexpressing High Molecular Weight FGF2 Isoforms

400 | Aug 05 2020

Liping Xiao et al. demonstrated that overexpression of the HMWFGF2 isoforms in preosteoblasts resulted in osteoarthropathy that couid be partially rescued by FGFR inhibitor via reduction in activated Wnt signaling. [Read the Full Post]

Comprehensive analyses of immunodynamics and immunoreactivity in response to treatment in ALK-positive non-small-cell lung cancer

407 | Aug 04 2020

Kyoung-Ho Pyo et al. found that ALK-positive tumors progressing on ceritinib was not immunogenic enough to respond to immune checkpoint inhibitors. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

0 | Jul 29 2020

Feng Li et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Epithelioid glioblastoma with microglia features: Potential for novel therapy

315 | Jul 28 2020

Nami Nakagomi et al. provided insight into the cellular nature of E-GBM and introduced several possibilities for effective targeted therapy for these patients. [Read the Full Post]

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

938 | Jul 22 2020

Cristina Saura et al.showed that N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. [Read the Full Post]

Critical role of SOX2-IGF2 signaling in aggressiveness of bladder cancer

278 | Jul 20 2020

Yu-Fan Chiu et al. indicated the SOX2-IGF2 signaling affected the aggressiveness of bladder cancer cell growth. [Read the Full Post]

IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells

276 | Jul 20 2020

Damiano Cosimo Rigiracciolo et al. suggested that the IGF-1/IGF-1R/FAK/YAP axis might contribute to the progression of the aggressive TNBC subtype. [Read the Full Post]

RAF dimer inhibition enhances the antitumor activity of MEK inhibitors in K-RAS mutant tumors

0 | Jul 18 2020

Xi Yuan et al. supported a vertical inhibition strategy in which RAF dimer and MEKi are combined to target K-RAS-mutated cancers. [Read the Full Post]

In vitro and in vivo efficacies of inhibitors of the EGFR/MEK/ERK signaling in the treatment of alveolar echinococcosis

665 | Jul 17 2020

Zhe Cheng et al. demonstrated the potential of EGFR-mediated signaling as a target for the development of novel anti-AE agents. [Read the Full Post]

A Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects

1208 | Jul 15 2020

Yiqing Yang et al. found that PROTACs showed better selectivity and less adverse effects than inhibitors, indicating that PROTACs had a great potential for overcoming clinical drug resistance and safety issues. [Read the Full Post]

Lenvatinib and Sorafenib for Differentiated Thyroid Cancer After Radioactive Iodine: A Systematic Review and Economic Evaluation

628 | Jul 13 2020

Nigel Fleeman et al.showed that compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. [Read the Full Post]

Discovery of Novel Dual c-Met/HDAC Inhibitors as a Promising Strategy for Cancer Therapy

633 | Jul 07 2020

Hao Hu et al. provided an efficient strategy for discovery of multitarget antitumor drugs. [Read the Full Post]

Efficacy of Gefitinib Combined With 125 I Radioactive Particles in the Treatment of Transplanted Lung Cancer Tumors in Nude Mice

703 | Jul 02 2020

Chaojie Li et al. found that Gefitinib combined with 125I radioactive particles brachytherapy could significantly inhibit tumor growth. [Read the Full Post]

MEK Inhibitors Combined With Programmed Cell death-1 Blockade Immunotherapy for Metastatic Uveal Melanoma: Is It Warranted?

479 | Jun 30 2020

Anais Zanella et al. highlighted the need to evaluate the safety and efficacy of new treatment options such as MEKi and anti-PD-1 for mUM. [Read the Full Post]

A New Compound With Increased Antitumor Activity by Cotargeting MEK and Pim-1

501 | Jun 30 2020

Yanan Li et al. uncovered a new MEK inhibitor KZ-02 with significantly enhanced antitumor activity by co-targeting MEK and Pim-1. [Read the Full Post]

Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E 2 Production

399 | Jun 24 2020

Filip Bergqvist et al. deployed a semi-high throughput and robust methodology to investigate anti-inflammatory properties of new chemical probes. [Read the Full Post]

RAF Dimer Inhibition Enhances the Antitumor Activity of MEK Inhibitors in K-RAS Mutant Tumors

834 | Jun 20 2020

Xi Yuan et al. supported a vertical inhibition strategy in which RAF dimer and MEKi are combined to target K-RAS-mutated cancers, and have led to a Phase 1b/2 combination therapy study of lifirafenib and mirdametinib in solid tumor patients with K-RAS mutations and other MAPK pathway aberrations. [Read the Full Post]

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

825 | Jun 19 2020

James Chih-Hsin Yang et al. found that Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutatios. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings. [Read the Full Post]

STMN1 Upregulation Mediates Hepatocellular Carcinoma and Hepatic Stellate Cell Crosstalk to Aggravate Cancer by Triggering the MET Pathway

677 | Jun 15 2020

Rui Zhang et al. suggested that STMN1 may be used as a potential marker to identify patients who may benefit from MET inhibitor treatment. [Read the Full Post]

Network Indirect Comparison of 3 BRAF + MEK Inhibitors for the Treatment of Advanced BRAF Mutated Melanoma

585 | Jun 12 2020

F Consoli et al. suggested a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM. [Read the Full Post]

AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells

399 | Jun 11 2020

Olivier Zajac et al. demonstrated that AXL controls directed cell migration most likely by regulating cell polarity. [Read the Full Post]

Combined Therapy of AXL and HDAC Inhibition Reverses Mesenchymal Transition in Diffuse Intrinsic Pontine Glioma

455 | Jun 11 2020

Michaël H Meel et al. found that combined inhibition of AXL and HDACs in DIPG cells results in a synergistic antitumor effect by reversing their mesenchymal, stem cell-like, therapy-resistant phenotype. [Read the Full Post]

Real-World Treatment Patterns and Progression-Free Survival Associated With Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

492 | Jun 08 2020

Mohammad Jahanzeb et al. found that median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first- and second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population. [Read the Full Post]

A Natural Anthraquinone Derivative Shikonin Synergizes With AZD9291 Against wtEGFR NSCLC Cells Through Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress

521 | Jun 01 2020

Xiu Hu et al. suggested that combining shikonin with AZD9291was a promising therapeutic strategy for treating wtEGFR NSCLC patients. [Read the Full Post]

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation With Favorable Pharmacokinetic Properties for Sustained in Vivo Pathway Inhibition

0 | May 26 2020

Aidan G Gilmartin et al. found that GSK1120212 combineed high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. [Read the Full Post]

Axl Inhibitor R428 Induces Apoptosis of Cancer Cells by Blocking Lysosomal Acidification and Recycling Independent of Axl Inhibition

438 | May 25 2020

Fangfang Chen et al. uncovered a novel function and mechanism of R428 in addition to its ability to inhibit Axl. [Read the Full Post]

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia

0 | May 25 2020

Isabel Ben-Batalla et al. showed that Axl inhibition had therapeutic potential in BCR-ABL TKI-sensitive as well as resistant CML and support the need for clinical trials. [Read the Full Post]

Early Long-Term Administration of the CSF1R Inhibitor PLX3397 Ablates Microglia and Reduces Accumulation of Intraneuronal Amyloid, Neuritic Plaque Deposition and Pre-Fibrillar Oligomers in 5XFAD Mouse Model of Alzheimer

342 | May 22 2020

Justyna Sosna et al. demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, was crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events were serially linked in a causal pathway leading to neurodegeneration and neuritic plaque formation. [Read the Full Post]

Pexidartinib: First Approval

416 | May 21 2020

Yvette N Lamb et al. summarized the milestones in the development of pexidartinib leading to its first approval for TGCT. [Read the Full Post]

Effects of PCI-32765 and Dasatinib on the Acute Lymphoblastic Leukemic Cells and Their Mechanisms

646 | May 20 2020

Yuan Deng et al. found that PCI-32765 or Dasatinib could inhibit the proliferation and induced the apoptosis of Sup-B15 and RS4;11 cells, PCI-32765 and Dasatinib displayed the synergistic effects. The possible mechanismmight be related with the blocking of B cell receptor(BCR) signal pathway, thereby inhibiting the cell proliferation and promoting the cell apoptosis. [Read the Full Post]

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib

438 | May 18 2020

Shankarappa PS et al. found that pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. [Read the Full Post]

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

524 | May 17 2020

Rendeiro AF et al. described time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL [Read the Full Post]

anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells

418 | May 10 2020

Liu S et al. demonstrated that PD-L1 high expression on VECs inhibits the infiltration of CD8+ T cells, whereas promotes the aggregation of FoxP3+ T cells into tumor tissues, thus becoming an "immunosuppressive barrier". Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth. [Read the Full Post]

A novel flow cytometry-based assay to measure compromised B cell receptor signaling as a prognostic factor in chronic lymphocytic leukemia

507 | May 06 2020

Heitmann JS et al. supported the role of compromised BCR signaling as an important prognostic marker in CLL and establish a novel diagnostic tool for its assessment in clinical settings. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI With Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

1148 | Apr 23 2020

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Design, Synthesis and Biological Evaluation of 2-amino-4-(1,2,4-triazol)pyridine Derivatives as Potent EGFR Inhibitors to Overcome TKI-resistance

542 | Apr 22 2020

Haikui Yang et al. provided 2-amino-4-(1,2,4-triazol)pyridines as a new scaffold for EGFRT790M and/or EGFRvⅢ inhibitor. [Read the Full Post]

The Syk Inhibitor R406 Is a Modulator of P-glycoprotein (ABCB1)-mediated Multidrug Resistance

542 | Apr 21 2020

George E Duran et al. indicated that the chemo-sensitizing effect of R406 in taxane-resistant cells previously reported was not associated with Syk but resulted from the modulation of P-gp-mediated MDR. [Read the Full Post]

Attenuated isolated 3' signal: A highly challenging therapy relevant ALK FISH pattern in NSCLC

481 | Apr 11 2020

Smuk G et al. indicated the adequate therapy with higher efficiency for patients suffering from NSCLC. [Read the Full Post]

Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis

583 | Apr 10 2020

Shah N et al. demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment. [Read the Full Post]

Sphingosine Kinase 1 in Breast Cancer-A New Molecular Marker and a Therapy Target

619 | Apr 09 2020

Alshaker H et al. concluded that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy. [Read the Full Post]

NTRK fusion-positive cancers and TRK inhibitor therapy

0 | Apr 05 2020

Cocco E D et al. discussed the biology of NTRK fusions, strategies to target these drivers in the treatment-naive and acquired-resistance disease settings, and the unique safety profile of TRK inhibitors. [Read the Full Post]

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

0 | Apr 01 2020

Cervantes-Madrid D et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study

571 | Mar 29 2020

Li Y et al. indicated that TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. [Read the Full Post]

Preclinical pharmacokinetics, disposition, and translational pharmacokinetic/pharmacodynamic modeling of savolitinib, a novel selective cMet inhibitor

376 | Mar 26 2020

Gu Y et al. supported clinical development of savolitinib. Understanding the preclinical PK/PD relationship of savolitinib provides translational insights into the cMet-targeted drug development. [Read the Full Post]

TFEB-mediated lysosomal biogenesis and lysosomal drug sequestration confer resistance to MEK inhibition in pancreatic cancer

482 | Mar 25 2020

Zhao B et al. showed accumulation of MEKi in the lysosomes of treated cells. [Read the Full Post]

Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia

660 | Mar 24 2020

Serafin V et al. suggested a quickly actionable approach to supporting conventional therapies and overcoming GC resistance in pediatric T-ALL patients. [Read the Full Post]

NTRK fusion-positive cancers and TRK inhibitor therapy

841 | Mar 23 2020

Cocco E et al. discussed the biology of NTRK fusions, strategies to target these drivers in the treatment-naive and acquired-resistance disease settings, and the unique safety profile of TRK inhibitors. [Read the Full Post]

The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice

436 | Mar 21 2020

Parikh SA et al. illustrated the challenges associated with continuous oral therapy with ibrutinib in patients with CLL. [Read the Full Post]

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

539 | Mar 21 2020

Rendeiro AF et al. described time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1073 | Mar 14 2020

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Molecular alterations and poziotinib efficacy, a pan-HER inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2-positive breast cancer patients

537 | Mar 11 2020

Koga T et al. identified HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2-positive MBC treated with poziotinib. [Read the Full Post]

Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study

633 | Mar 10 2020

Koga T et al. identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

987 | Mar 09 2020

Torres-Hernandez A et al. suggested that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice

456 | Mar 08 2020

Llop-Guevara A et al. showed that concurrent JAK + SYK inhibition resulted in higher efficacy than single kinase inhibition and TNF blockade in a chronic and severe arthritis model. Thus, blockade of multiple immune signals with dual JAK + SYK inhibition represents a reasonable therapeutic strategy for RA, in particular in patients with inadequate responses to current treatments. Our data supports the multiplicity of events underlying this heterogeneous and complex disease. [Read the Full Post]

Phase I Dose-Escalation Study of the pan-HER Inhibitor, PF299804, in Patients With Advanced Malignant Solid Tumors

564 | Mar 02 2020

Pasi A Jänne et al. showed the MTD of PF299804 is 45 mg/d. Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients. [Read the Full Post]

The Syk Inhibitor Fostamatinib Disodium (R788) Inhibits Tumor Growth in the Eμ- TCL1 Transgenic Mouse Model of CLL by Blocking Antigen-Dependent B-cell Receptor Signaling

743 | Feb 26 2020

Mirza Suljagic et al. provided further rationale for clinical trials with R788 in CLL and establish the BCR-signaling pathway as an important therapeutic target in this disease. [Read the Full Post]

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

555 | Feb 25 2020

McDermott DF et al. suggested that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

1447 | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

0 | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study

616 | Feb 16 2020

Xu F et al. showed that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [Read the Full Post]

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

907 | Feb 07 2020

Casavecchia G et al. reported and discussed most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. [Read the Full Post]

CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant

492 | Feb 04 2020

Sakamoto H et al. supported the potential for clinical evaluation of CH5424802 for the treatment of patients with ALK-driven tumors. [Read the Full Post]

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

623 | Feb 03 2020

Tong X et al. suggested that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC. [Read the Full Post]

PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy in a cardiac arrest rat model

427 | Feb 03 2020

Zheng JH et al. showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. [Read the Full Post]

Treatment outcome and clinical characteristics of HER2 mutated advanced non-small cell lung cancer patients in China

617 | Feb 01 2020

Fei Xu et al. found that HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype. [Read the Full Post]

Determination of Somatic Mutations and Tumor Mutation Burden in Plasma by CAPP-Seq during Afatinib Treatment in NSCLC Patients Resistance to Osimertinib

752 | Feb 01 2020

Ishii H et al. demonstrated that detection of mutant allele frequency and TMB of ctDNA by CAPP-Seq could help determine the effectiveness of and resistance to afatinib. [Read the Full Post]

The small molecule AZD6244 inhibits dengue virus replication in vitro and protects against lethal challenge in a mouse model

423 | Jan 30 2020

de Oliveira LC et al. demonstrated the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases. [Read the Full Post]

MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway

458 | Jan 30 2020

Nan P et al. found that MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway. [Read the Full Post]

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27

496 | Jan 29 2020

Fu H et al. found that tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy. [Read the Full Post]

Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)

606 | Jan 25 2020

Yang PW et al. demonstrated that both cabozantinib and R428 inhibit ESCC growth in cell and xenograft models. The results reveal the great potential of using cabozantinib for targeted therapy of ESCC. [Read the Full Post]

Molecular therapies and precision medicine for hepatocellular carcinoma

603 | Jan 23 2020

Llovet JM et al. summarized the molecular targets and therapies for the management of HCC and discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies. [Read the Full Post]

CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib

0 | Jan 22 2020

Jetani H et al. provided the first proof-of-concept that CAR T-cell immunotherapy and small molecule inhibition can be used synergistically, as exemplified by our data showing superior antileukemia efficacy of FLT3-CAR T-cells in combination with crenolanib. [Read the Full Post]

Characteristics of Patients With ROS1+ Cancers: Results From the First Patient-Designed, Global, Pan-Cancer ROS1 Data Repository

1058 | Dec 30 2019

This study is the first global, patient-designed approach, to our knowledge, to comprehensively assess demographic, clinical, and environmental characteristics associated with ROS1+ cancers. [Read the Full Post]

Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)

464 | Dec 27 2019

Yang PW et al. revealed the great potential of using cabozantinib for targeted therapy of ESCC. [Read the Full Post]

Highly accurate DNA-based detection and treatment results of MET exon 14 skipping mutations in lung cancer

973 | Dec 27 2019

Pruis MA et al. showed that METex14del can be reliably detected by routine DNA NGS analysis. [Read the Full Post]

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580

0 | Dec 25 2019

Conway JG et al. indicated that GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. [Read the Full Post]

The development of HKI-272 and related compounds for the treatment of cancer

691 | Dec 22 2019

Wissner A et al. highlight the findings that these irreversible inhibitors retain activity against tumors that have acquired a resistance to the reversible binding inhibitors gefitinib and erlotinib. The promising interim clinical trial results for HKI-272 and EKB-569 in treating colon, lung, and breast cancers are summarized. [Read the Full Post]

miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells

594 | Dec 16 2019

Mazzu YZ et al. indicated that miR-193b not only functions as a tumor suppressor in liposarcoma but also promotes adipogenesis in ASC. Furthermore, this study reveals key tyrosine kinase and DNA methylation pathways in liposarcoma, some with immediate implications for therapeutic exploration. [Read the Full Post]

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies

0 | Dec 14 2019

Li J et al. demonstrated that quizartinib potentiates the antineoplastic activity of wild-type and R482T mutant ABCG2 substrates. These findings may be useful in clinical practice for cancer combination therapy with quizartinib. [Read the Full Post]

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

0 | Dec 14 2019

Van Cutsem E et al. showed that AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated. [Read the Full Post]

Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells

988 | Dec 10 2019

Kuntz EM et al. provided a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease. [Read the Full Post]

Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo

0 | Dec 03 2019

Xue C et al. indicated that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. [Read the Full Post]

U0126 attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway

516 | Nov 20 2019

Wang A et al. suggested that U0126 may protect against H/R injury by preventing H/R-induced myocardium apoptosis and autophagy via the MEK/ERK/EGR-1 pathway, and may be a potential therapeutic approach for attenuating myocardial I/R injury. [Read the Full Post]

PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts

395 | Nov 20 2019

Choo EF et al. suggested that, based on minimal data, it is possible to predict the effects of various combinations preclinically and also assess the potential clinical efficacy of combinations using human pharmacokinetic inputs. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

0 | Nov 19 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

497 | Nov 18 2019

McGivern N et al. provided a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials. [Read the Full Post]

PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines

509 | Nov 17 2019

Nakachi I et al. indicated PTTG1 may be a valuable biomarker in ovarian cancer to predict sensitivity to saracatinib, and could form the basis of a targeted prospective saracatinib trial for ovarian cancer. [Read the Full Post]

Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats

487 | Nov 16 2019

Hirschi KM et al.provided insight into pathways associated with PE that could be useful in the clarification of potential therapeutic approaches. [Read the Full Post]

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity

403 | Nov 05 2019

Bernstein A et al. found that Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events. [Read the Full Post]

Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials

489 | Nov 04 2019

Zhou Y et al. aimed to compare the adverse drug events which were associated with the use of ibrutinib for the treatment of patients with CLL. [Read the Full Post]

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab

389 | Nov 04 2019

Moser JC et al. found that patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi. [Read the Full Post]

Itraconazole increases ibrutinib exposure ten-fold and reduces inter-individual variation - A potentially beneficial drug-drug interaction

512 | Nov 03 2019

Tapaninen T et al. found that itraconazole markedly increases ibrutinib bioavailability and decreases its inter-individual variability, offering a possibility to improved dosing accuracy and cost savings. [Read the Full Post]

The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models

714 | Nov 02 2019

Zhang S et al. provided the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. [Read the Full Post]

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

544 | Oct 18 2019

Komla-Ebri D et al. demonstrated that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH. [Read the Full Post]

Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC

896 | Oct 18 2019

Wei L et al. demonstrated that targeting PHGDH is an effective approach to overcome TKI drug resistance in HCC. [Read the Full Post]

Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma

714 | Oct 17 2019

Javle M et al. indicated that BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population. [Read the Full Post]

Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors

646 | Oct 16 2019

Nishio M et al. indicated that ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing. [Read the Full Post]

Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis

735 | Oct 15 2019

Ruprecht B et al. offered deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

732 | Oct 09 2019

Li F et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Multicellular gene network analysis identifies a macrophage-related gene signature predictive of therapeutic response and prognosis of gliomas

337 | Oct 08 2019

Sun X et al. identified macrophage-related gene signature has good prognostic value for predicting resistance to targeted therapeutics and survival of glioma patients, implying that combining current targeted therapies with new macrophage-targeted therapy may be beneficial for the long-term treatment outcomes of glioma patients. [Read the Full Post]

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

808 | Oct 05 2019

Li D et al. showed that BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms. Consistent with this activity, BIBW2992 suppresses transformation in isogenic cell-based assays, inhibits survival of cancer cell lines and induces tumor regression in xenograft and transgenic lung cancer models, with superior activity over erlotinib. These findings encourage further testing of BIBW2992 in lung cancer patients harboring EGFR or HER2 oncogenes. [Read the Full Post]

Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor

511 | Sep 29 2019

Mulvihill MJ et al. showed that OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing. [Read the Full Post]

Overcoming Linsitinib intrinsic resistance through inhibition of nuclear factor-κB signaling in esophageal squamous cell carcinoma

854 | Sep 26 2019

Wu J et al. demonstrated that the intrinsic resistance to Linsitinib was predominantly mediated by NF-κB activation in ESCC. Moreover, combination of Linsitinib and JSH-23 as therapy provides a novel strategy to overcome resistance to Linsitinib in ESCC. [Read the Full Post]

Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models

1131 | Sep 23 2019

Gozgit JM et al. showed that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers. [Read the Full Post]

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts

0 | Sep 22 2019

Wiegering A et al. suggested antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS. [Read the Full Post]

Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth

587 | Sep 15 2019

Yakes FM et al. suggested that cabozantinib is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling. [Read the Full Post]

Effective combinatorial immunotherapy for castration-resistant prostate cancer

0 | Sep 15 2019

Lu X et al. illuminated a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of mCRPC. [Read the Full Post]

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia

528 | Sep 14 2019

Erdmann R et al. showed that Axl inhibition has therapeutic potential in BCR-ABL TKI-sensitive as well as -resistant CML and support the need for clinical trials. [Read the Full Post]

ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy

685 | Sep 03 2019

Wakeling AE et al. indicated the potential utility of ZD1839 in the treatment of many human tumors and indicate that continuous once-a-day p.o. dosing might be a suitable therapeutic regimen. [Read the Full Post]

Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas

480 | Sep 01 2019

Dombi E et al. suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. [Read the Full Post]

A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study

431 | Sep 01 2019

Banerjee A et al. indicated that selumetinib has promising antitumor activity in children with LGG. Rash and mucositis were the most common DLTs. [Read the Full Post]

Inhibition of glioblastoma dispersal by the MEK inhibitor PD0325901

448 | Aug 21 2019

Shannon S et al. showed that PD0325901 significantly increases aggregate cohesion, stiffness, and viscosity but only when tumor cells have access to high concentrations of fibronectin. Treatment also results in reorganization of actin from cortical into stress fibers, in both 2D and 3D culture. Moreover, drug treatment localized pFAK at sites of cell-substratum adhesion. Collectively, these changes resulted in increased strength of substrate attachment and decreased motility, a decrease in aggregate dispersal velocity, and in a marked decrease in growth rate of both 2D and 3D cultures. [Read the Full Post]

Brief Report: Rapid Acquisition of Alectinib Resistance in ALK-positive Lung Cancer with High Tumor Mutation Burden

552 | Aug 16 2019

Makimoto G et al. found that high TMB and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

806 | Aug 15 2019

Noronha V et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Yiqi Chutan Tang Reduces Gefitinib-Induced Drug Resistance in Non-Small-Cell Lung Cancer by Targeting Apoptosis and Autophagy

678 | Aug 15 2019

Zhang J et al. provided a new treatment strategy for patients with EGFR-TKI resistance in NSCLC. [Read the Full Post]

Treatment Patterns in Patients with Chronic-Phase Chronic Myeloid Leukaemia in Routine Clinical Practice: the SIMPLICITY Italian Population

1443 | Aug 10 2019

Abruzzese E et al. provided valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice. [Read the Full Post]

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations

1138 | Aug 05 2019

Zou HY et al. indicated that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. [Read the Full Post]

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors

453 | Aug 03 2019

Wesolowski R et al. showed the combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration. [Read the Full Post]

Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation

664 | Jul 25 2019

Shi P et al. showed that modulation of MEK/ERK-dependent Bim and Mcl-1 degradation critically mediates sensitivity and resistance of EGFR-mutant NSCLC cells to AZD9291 and hence is an effective strategy to overcome acquired resistance to AZD9291. [Read the Full Post]

GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition

830 | Jul 21 2019

Gilmartin AG et al. showed that GSK1120212 combines high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. [Read the Full Post]

Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs

403 | Jul 18 2019

Patwardhan PP et al. suggested that PLX3397 is superior to imatinib in the treatment of MPNSTs, and the combination of PLX3397 with a TORC1 inhibitor could provide a new therapeutic approach for the treatment of this disease. [Read the Full Post]

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

575 | Jul 16 2019

Honigberg LA et al. support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway. [Read the Full Post]

Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study

700 | Jul 07 2019

Fennell DA et al. indicated that neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinibcannot be recommended as maintenance therapy for advanced MPM. [Read the Full Post]

A high-performance liquid chromatography-tandem mass spectrometry method for the determination of lifrafenib, a novel RAF kinase and EGFR inhibitor, in human plasma and urine and its application in clinical pharmacokinetic study

763 | Jul 01 2019

Yao X et al. showed robust and sensitive, it successfully fulfilled the requirement of clinical pharmacokinetic study of lifirafenib in Chinese patients with locally advanced or metastatic solid tumors. [Read the Full Post]

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

856 | Jun 30 2019

Tran P et al. presented the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. [Read the Full Post]

First-in-Human Phase I Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics, and Antitumor Activity

433 | Jun 30 2019

Gan HK et al. showed the tolerability profile of savolitinib was acceptable and the RP2D was established as 600 mg QD. Preliminary antitumor activity was demonstrated supporting further study in patients with PRCC. [Read the Full Post]

Fibroblast Growth Factor Receptor 4 Targeting in Cancer: New Insights into Mechanisms and Therapeutic Strategies

657 | Jun 28 2019

Lang L et al. indicated their aim is to pinpoint the potential of FGFR4 as a therapeutic target and identify new avenues for advancing future research in the field. [Read the Full Post]

TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response

950 | Jun 21 2019

Sener Y et al. concluded that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis. [Read the Full Post]

A DSTYK mutation activates ERK1/2 signaling to promote intraspinal dissemination in a case of solitary fibrous tumor/hemangiopericytoma

549 | Jun 18 2019

Tang G et al. revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease. [Read the Full Post]

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

873 | Jun 18 2019

Huang F et al. indicated the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells. [Read the Full Post]

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

908 | Jun 12 2019

Huang WS et al. showed that brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial. [Read the Full Post]

Trametinib Induces Neurofibroma Shrinkage and Enables Surgery

504 | Jun 11 2019

Vaassen P et al. suggested that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1. [Read the Full Post]

NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors

814 | Jun 08 2019

Park HR et al. suggested that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC. [Read the Full Post]

Regulation of cisplatin-resistant head and neck squamous cell carcinoma by the SRC/ETS-1 signaling pathway

469 | Jun 06 2019

Yang Z et al. demonstrated that the SRC/ETS-1 pathway plays a crucial role and could be a key therapeutic target in cisplatin-resistant HNSCC treatment. [Read the Full Post]

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580

436 | Jun 04 2019

Conway JG et al. showed that GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. [Read the Full Post]

ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial

1033 | Jun 02 2019

Gorcea CM et al. showed that ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). [Read the Full Post]

A novel anti-melanoma SRC-family kinase inhibitor.

535 | May 24 2019

Halaban R suggested that the new compound could be used in the clinic as a substitute for, or in combination with MAPK inhibitors. [Read the Full Post]

Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial

839 | May 07 2019

Shaw AT et al. indicated lorlatinib might be an effective therapeutic strategy for patients with ALK-positive NSCLC who have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised controlled trial comparing lorlatinib to crizotinib (ClinicalTrials.gov, NCT03052608). [Read the Full Post]

Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

871 | Apr 24 2019

Pinato DJ et al. found that suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance. [Read the Full Post]

Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance

664 | Apr 24 2019

Xu H et al. found that long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients. [Read the Full Post]

High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma

729 | Apr 14 2019

Wang S et al. indicated that FAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma. [Read the Full Post]

lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling

0 | Apr 10 2019

Lu Y et al. described a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These findings identify a clinically actionable, epigenetic cause of cetuximab resistance. [Read the Full Post]

Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial

624 | Apr 03 2019

Planchard D et al. found that Dabrafenib plus trametinib represents a new therapy with clinically meaningful antitumour activity and a manageable safety profile in patients with previously untreated BRAFV600E-mutant NSCLC. [Read the Full Post]

Ibrutinib for the treatment of chronic lymphocytic leukemia

710 | Mar 30 2019

Novel, extremely promising, combination strategies, based on the association of ibrutinib with chemoimmunotherapy, antiCD20 monoclonal antibody or other targeted agents, are currently being investigated, with the goal of achieving greater depth of remission, especially MRD-negativity, and removing the need for indefinite treatment. [Read the Full Post]

Lenvatinib versus placebo in radioiodine-refractory thyroid cancer

814 | Mar 25 2019

Schlumberger M et al. indicated that Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. [Read the Full Post]

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts

692 | Mar 25 2019

Wiegering A et al. suggested antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS. [Read the Full Post]

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials

869 | Mar 20 2019

Tao Z et al. demonstrated that neratinib provides a benefit in survival outcome. When combined with other anticancer agents, neratinib may hold promise for treating breast cancer with central nervous system metastases. [Read the Full Post]

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

1078 | Mar 19 2019

Martin M et al. showed that at the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

803 | Mar 07 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies

746 | Mar 05 2019

Li J et al. demonstrated that quizartinib potentiates the antineoplastic activity of wild-type and R482T mutant ABCG2 substrates. These findings may be useful in clinical practice for cancer combination therapy with quizartinib. [Read the Full Post]

Risk of anastomotic dehiscence in patients with pulmonary fibrosis transplanted while receiving anti-fibrotics: Experience of the Australian Lung Transplant Collaborative

820 | Mar 04 2019

Mackintosh JA et al. showed the incidence of bronchial dehiscence after transplantation for IPF is low and is not significantly higher in patients receiving anti-fibrotic therapy at the time of transplantation. [Read the Full Post]

Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo

938 | Mar 04 2019

Xue C et al. indicated that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. [Read the Full Post]

Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination

479 | Feb 25 2019

Wies Mancini VSB et al. showed that BLZ945 induced a significant reduction in the number of microglia. Preventive BLZ945 treatment attenuated demyelination in the acute CPZ model, mainly in cortex and external capsule. In contrast, BLZ945 treatment in the acute CPZ model failed to protect myelin or foster remyelination in myelin-rich areas, which may respond to a loss in microglial phagocytic capacity and the consequent impairment in oligodendroglial differentiation. Preventive and therapeutic BLZ945 treatment promoted remyelination and neuroprotection in the chronic model. These results could be potentially transferred to the treatment of progressive forms of MS. [Read the Full Post]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

2863 | Feb 24 2019

Abdelhafez OM et al. indicated these promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness. [Read the Full Post]

Crenolanib is a selective type I pan-FLT3 inhibitor

695 | Feb 21 2019

Smith CC et al. showed that Crenolanib has significant promise for achieving deep and durable responses in FLT3-mutant AML, and may have a profound impact upon future medicinal chemistry efforts in oncology. [Read the Full Post]

Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in Metastatic colorectal cancer - An Indian exploratory analysis study

927 | Feb 19 2019

Ramaswamy A et al. indicated duration of treatment with regorafenib as an efficacy end point in this study is similar to available data from other regions as it is the side effect profile. [Read the Full Post]

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

1168 | Feb 18 2019

Bruix J et al. indicated that regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

0 | Feb 10 2019

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium

694 | Feb 06 2019

Huang J et al. identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. [Read the Full Post]

The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

431 | Feb 06 2019

Chen L et al. demonstrated that the energy-sensing LKB1-AMPK pathway regulates IGF1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF1R-PKB pathway. [Read the Full Post]

Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms

512 | Jan 26 2019

Diamond EL et al. highlighted the importance of comprehensive genomic analysis of these disorders. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

1484 | Jan 22 2019

Suttorp M et al. indicated that adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

0 | Jan 22 2019

Suttorp M et al. indicated taht pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug-drug/food-drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. [Read the Full Post]

MEK inhibitor, PD98059, promotes breast cancer cell migration by inducing β-catenin nuclear accumulation

1319 | Jan 21 2019

Zhao Y et al. may elucidate a possible mechanism explaining the ineffectiveness of MEK inhibitors in breast cancer treatment and improve our understanding of the role of MEK in cancer. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Jan 19 2019

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

997 | Jan 15 2019

Van Cutsem E et at. indicated that AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated. [Read the Full Post]

The c.1085A>G Genetic Variant of CSF1R Gene Regulates Tumor Immunity by Altering the Proliferation, Polarization, and Function of Macrophages

477 | Nov 26 2018

Yeh YM et al. indicated that CSF1R c.1085A>G genetic variant regulates tumor immunity by altering the polarization and function of macrophages. This genetic variant confers the sensitivity to CSF-1R inhibitors, implying as a biomarker in targeting CSF-1R signaling for cancer treatment. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

6040 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

Oncogenic KRas-induced Increase in Fluid-phase Endocytosis is Dependent on N-WASP and is Required for the Formation of Pancreatic Preneoplastic Lesions

597 | Nov 17 2018

Lubeseder-Martellato C et al. defined a new role of FPE as a tumor initiating mechanism. [Read the Full Post]

The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis

778 | Nov 16 2018

Solis NV et al. indicated that AhR plays a central role in governing the pathogenic interactions of C. albicans with oral epithelial cells during OPC and suggested that this receptor is a potential therapeutic target [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

1438 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

2016 | Nov 11 2018

Lee S et al indicated that sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. [Read the Full Post]

Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout

621 | Nov 09 2018

Liu L et al. revealed that IL-37 limits runaway inflammation initiated by MSU crystal-induced immune responses, partly in a Mertk-dependent fashion. Thus, rhIL-37 has both preventive and therapeutic effects in gouty arthritis. [Read the Full Post]

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

1014 | Nov 07 2018

Feng X et al. illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis. This double-edged role of caspase 3 suggested that taming caspase 3 from the opposite side, not always activating it, may provide novel therapeutic strategies due to restricted post-irradiation angiogenesis. [Read the Full Post]

The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling

0 | Nov 07 2018

Booth L et al. indicated that inhibition of ERBB3 signaling via both blockade of SRC and ERBB1 results in tumor cell death. [Read the Full Post]

Pro-survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia

0 | Nov 06 2018

Chen Y et al. showed that dinaciclib targets multiple pro-survival signalling pathways in CLL, which provides a mechanistic explanation for its potent induction of apoptosis. They also support a therapeutic application of cyclin-dependent kinase inhibitors in CLL in combination with other relevant targeted therapies. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

1045 | Nov 06 2018

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

0 | Nov 04 2018

Peterse EF et al. indicated that the IGF pathway is not essential for chondrosarcoma growth, migration or chemoresistance. Furthermore, IGF1R is only minimally expressed in chondrosarcoma primary tumours. Therefore, the IGF pathway is not expected to be an effective therapeutic target for chondrosarcoma of bone. [Read the Full Post]

Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity

816 | Nov 01 2018

Hutterer C et al. concluded that DYRK signaling represents a promising target pathway for the development of novel anti-herpesviral strategies. [Read the Full Post]

Steroid hormone 20-hydroxyecdysone promotes higher calcium mobilization to induce apoptosis

900 | Oct 31 2018

Wang D et al. suggested that 20E and JH via different pathways regulate calcium mobilization and homeostasis at different levels, thus inform different gene expression and cellular responses. [Read the Full Post]

DYRK1B blocks canonical and promotes non-canonical Hedgehog signaling through activation of the mTOR/AKT pathway

838 | Oct 31 2018

Singh R et al. showed that a pharmacological approach combining a DYRK1B antagonist with an mTOR/AKT inhibitor results in strong GLI1 targeting and in pronounced cytotoxicity in human pancreatic and ovarian cancer cells. [Read the Full Post]

Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle

759 | Oct 30 2018

Tan H et al. indicated that TSU-68 relaxes tense ASM by reducing the intracellular Ca2+ concentration through blocking VDCCs and NSCCs, which suggested that this small molecule might be useful in the treatment of abnormal smooth muscle. [Read the Full Post]

MET amplification and epithelial-to-mesenchymal transition exist as parallel resistance mechanisms in erlotinib-resistant, EGFR-mutated, NSCLC HCC827 cells

579 | Oct 27 2018

Jakobsen KR et al. showed that parallel resistance mechanisms appear during erlotinib-resistance development in EGFR-mutated NSCLC cells and highlight a role for FGFR1 expression changes as an early response to erlotinib as well as a bypass-signaling mechanism. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

1001 | Oct 25 2018

Ramirez M et al. found that the drug-tolerant persister state does not limit--and may even provide a latent reservoir of cells for--the emergence of heterogeneous drug-resistance mechanisms. [Read the Full Post]

Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro

741 | Oct 23 2018

Kim S et al. not only revealed critical but unappreciated role of mechanical cue that regulates lymphangiogenic sprouting, but also provides a novel biomimetic model that may leverage further biological studies as well as phenotypic drug screening. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

1674 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

PDE5 inhibitors enhance the lethality of [pemetrexed + sorafenib]

1238 | Oct 19 2018

Booth L et al. argued that additional clinical studies combining pemetrexed, sorafenib and sildenafil are warranted. [Read the Full Post]

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

909 | Oct 18 2018

Guo H et al. proposed that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2. [Read the Full Post]

The selective MEK1 inhibitor Selumetinib enhances the antitumor activity of everolimus against renal cell carcinoma in vitro and in vivo

575 | Oct 17 2018

Zou Y et al. provided a sound evidence that combination of everolimus and Selumetinib is a potential dual-targeted strategy for renal cell carcinoma. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1829 | Oct 12 2018

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells

579 | Oct 10 2018

Wang YQ et al. indicated that FS-108 is a powerful agent that impacts the survival of gefitinib-resistant cells in vitro and in vivo through targeting Hsp90. [Read the Full Post]

Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system

930 | Oct 08 2018

Jiang Y et al. demonstrated that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 01 2018

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. [Read the Full Post]

Efficient extravasation of tumor-repopulating cells depends on cell deformability

795 | Sep 30 2018

Chen J et al. suggested that tumor cell deformability is a key factor in controlling extravasation dynamics during metastasis. [Read the Full Post]

Pre-Osteoblasts Stimulate Migration of Breast Cancer Cells via the HGF/MET Pathway

608 | Sep 28 2018

Vallet S et al. demonstrated for the first time a role for pre-OBs in mediating HGF/MET- dependent migration of BC cells and strongly support the clinical evaluation of INCB28060 and other MET inhibitors to limit and/or prevent BC-associated bone metastases. [Read the Full Post]

Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties

725 | Sep 28 2018

Les F et al.found that piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it. [Read the Full Post]

Efficacy of focal adhesion kinase inhibition in non-small cell lung cancer with oncogenically activated MAPK pathways

1042 | Sep 27 2018

Zhang H, et al. demonstrated efficacy both in vitro and in vivo in lung cancers with either oncogenic RAS or EGFR mutations. In addition, FAK inhibition in combination with inhibitors of Bcl-2 family of anti-apoptotic proteins has synergistic activity in these MAPK-activated non-small cell lung cancer cell line models. [Read the Full Post]

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

908 | Sep 27 2018

Batista de Carvalho AL et al. aimed at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials. [Read the Full Post]

Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A

2656 | Sep 26 2018

Pelillo C et al. supported the new concept that metal-based drugs can inhibit tumour metastases through targeting of integrins and of other proteins which mediate tumour progression-related cell functions such as adhesion and migration. [Read the Full Post]

RAD51 inhibition in triple negative breast cancer cells is challenged by compensatory survival signaling and requires rational combination therapy

0 | Sep 25 2018

Wiegmans AP et al. highlight a potential compensatory mechanism via p38 that limits DNA targeted therapy. [Read the Full Post]

Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis

0 | Sep 25 2018

Oppliger J et al. revealed novel fundamental aspects of the LASV-host cell interaction and highlights a possible candidate drug target for therapeutic intervention. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

0 | Sep 24 2018

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

Antibiotic drug tigecycline reduces neuroblastoma cells proliferation by inhibiting Akt activation in vitro and in vivo

781 | Aug 24 2018

Zhong X et al. supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

638 | Aug 23 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells

1499 | Aug 22 2018

Luo LX et al. indicated these results broaden our understanding of the mechanisms on honokiol effects in lung cancer, and reinforce the possibility of its potential anticancer benefit as a popular Chinese herbal medicine (CHM). [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

0 | Aug 20 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers

617 | Aug 15 2018

Lock R et al. demonstrated that combined MNK and MEK suppression represents a promising therapeutic strategy for these incurable Ras-driven tumors and highlight the utility of developing selective MNK inhibitors for these and possibly other malignancies. [Read the Full Post]

The cKit Inhibitor, Masitinib, Prevents Diabetes-Induced Retinal Vascular Leakage

1046 | Aug 10 2018

Kim SR et al. provided the first demonstration that cKit inhibitors, such as masitinib, might be promising therapeutics for prevention of diabetes-induced breakdown of the BRB. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

0 | Aug 10 2018

Rebouissou S et al. indicated that Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

Local release of masitinib alters in vivo implantable continuous glucose sensor performance

918 | Aug 09 2018

Avula M et al. showed that the mast cell-targeting tyrosine kinase inhibitor, masitinib, was released from degradable polymer microspheres delivered from the surfaces of FDA-approved human commercial CGM needle-type implanted sensors in a rodent subcutaneous test bed. By targeting the mast cell c-Kit receptor and inhibiting mast cell activation and degranulation, local masitinib penetration around the CGM to several hundred microns sought to reduce sensor fibrosis to extend CGM functional lifetimes in subcutaneous sites. Drug-releasing and control CGM implants were compared in murine percutaneous implant sites for 21 days using direct-wire continuous glucose reporting. Drug-releasing implants exhibited no significant difference in CGM fibrosis at implant sites but showed relatively stable continuous sensor responses over the study period compared to blank microsphere control CGM implants. [Read the Full Post]

Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis

0 | Aug 09 2018

Sun X et al. showed that metallothionein (MT)-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. [Read the Full Post]

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

1202 | Aug 02 2018

Gao SP et al. revealed a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

1400 | Aug 01 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation

1101 | Jul 20 2018

Grassilli E et al. revealed that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach. [Read the Full Post]

BTK inhibition is a potent approach to block IgE-mediated histamine release in human basophils

1058 | Jul 19 2018

Smiljkovic D et al. indicated that BTK-targeting drugs are potent inhibitors of IgE-dependent histamine release in human basophils. The clinical value of BTK inhibition in the context of allergic diseases remains to be determined. [Read the Full Post]

Src family kinases promote silencing of ATR-Chk1 signaling in termination of DNA damage checkpoint.

925 | Jul 07 2018

Fukumoto Y, et al. suggested a model according to which Src family kinases send a termination signal between the completion of DNA repair and the initiation of checkpoint termination. [Read the Full Post]

Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells

872 | Jul 01 2018

Li H et al. indicated that the results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions. [Read the Full Post]

Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma

0 | Jun 30 2018

Mao Y et al. demonstrated the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its clinical potential as an immunotherapy for human cancers. [Read the Full Post]

FcγRIIB mediates antigen-independent inhibition on human B lymphocytes through Btk and p38 MAPK

1018 | Jun 29 2018

Tzeng SJ et al. found the importance of antigen-independent inhibition by FcγRIIB in the prevention from antibody-mediated autoimmune diseases and in the regulation of B cell homeostasis. [Read the Full Post]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

1912 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

2136 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [Read the Full Post]

RAD51 inhibition in triple negative breast cancer cells is challenged by compensatory survival signaling and requires rational combination therapy

684 | Jun 13 2018

Wiegmans AP et al. highlight a potential compensatory mechanism via p38 that limits DNA targeted therapy. [Read the Full Post]

EGF-mediated EGFR/ERK signaling pathway promotes germinative cell proliferation in Echinococcus multilocularis that contributes to larval growth and development

1644 | Jun 08 2018

Cheng Z et al. demonstrated the contribution of EGF-mediated EGFR/ERK signaling to the regulation of germinative cells in E. multilocularis, and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis. [Read the Full Post]

FcγRIIB-Independent Mechanisms Controlling Membrane Localization of the Inhibitory Phosphatase SHIP in Human B Cells

874 | Jun 02 2018

Pauls SD et al. indicated that FcγRIIB is not uniquely able to promote membrane recruitment of SHIP, but rather modulates its function via formation of distinct signaling complexes. [Read the Full Post]

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases

1639 | May 28 2018

Song X et al. provided insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. [Read the Full Post]

Smooth muscle cell-specific Tgfbr1 deficiency promotes aortic aneurysm formation by stimulating multiple signaling events

737 | May 24 2018

Yang P et al. indicated that loss of SMC-Tgfbr1 triggers multiple deleterious pathways, including abnormal TGFBR2, ERK, and AngII/AT1R signals that disrupt aortic wall homeostasis to cause aortic aneurysm formation. [Read the Full Post]

Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines

804 | May 23 2018

Fernández ML et al. showed the greatest anti-proliferative effects. This study serves as a basis for much needed future research on MEKi drug efficacy in LGSC. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Cell-based approach for 3D reconstruction of lymphatic capillaries in vitro reveals distinct functions of HGF and VEGF-C in lymphangiogenesis

804 | May 14 2018

Gibot L et al. showed that fibroblast-derived VEGF-C and HGF cooperate in the formation of lymphatic vasculature by activating ERK1/2 signaling, and demonstrate distinct functions of HGF/c-Met and VEGF-C/VEGFR-3 in lymphangiogenesis. This lymphatic vascular construct is expected to facilitate studies of lymphangiogenesis in vitro and it holds promise as a strategy for regeneration of lymphatic vessels and treatment of lymphatic disorders in various conditions. [Read the Full Post]

miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting MET

848 | May 14 2018

Chen QY et al. found that miR-206 could also sensitize A549/DDP cells to cisplatin in mice model. Taken together, our study implied that activation of miR-206 or inactivation of its target gene pathway could serve as a novel approach to reverse cisplatin resistance in lung adenocarcinomas cells. [Read the Full Post]

Therapeutic implication of HER2 in advanced biliary tract cancer

1472 | May 10 2018

Nam AR et al. suggested that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. [Read the Full Post]

Identification of different ALK mutations in a pair of neuroblastoma cell lines established at diagnosis and relapse

1157 | May 02 2018

Chen L et al. showed that use both Sanger and targeted deep sequencing, this study describes the identification of distinct ALK mutations in these paired cell lines, including the rare R1275L mutation, which has not previously been reported in a neuroblastoma cell line. Analysis of the sensitivity of NBLW and NBLW-R cells to a panel of ALK inhibitors (TAE-684, Crizotinib, Alectinib and Lorlatinib) revealed differences between the paired cell lines, and overall NBLW-R cells with the F1174L mutation were more resistant to ALK inhibitor induced apoptosis compared with NBLW cells. This pair of cell lines represents a valuable pre-clinical model of clonal evolution of ALK mutations associated with neuroblastoma progression. [Read the Full Post]

Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2

1176 | May 01 2018

Gnani D et al. demonstrated that FAK depletion reduces HCC cell growth by affecting cancer-promoting genes including the pro-oncogene EZH2. Furthermore, we unveil a novel unprecedented FAK/EZH2 crosstalk in HCC cells, thus identifying a targetable network paving the way for new anticancer therapies. [Read the Full Post]

A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced Osteoblast Differentiation In Vitro

2356 | Apr 29 2018

Lee Y et al. suggested that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders. [Read the Full Post]

Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells

1893 | Apr 29 2018

Chon HJ et al. provided new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. [Read the Full Post]

Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma

850 | Apr 28 2018

Mao Y et al. demonstrated the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its [Read the Full Post]

PQ401, an IGF-1R inhibitor, induces apoptosis and inhibits growth, proliferation and migration of glioma cells

737 | Apr 26 2018

Zhou X et al. suggested that PQ401 may serve as a promising leading drug for treating glioma patients with elevated IGF-1R signalling. [Read the Full Post]

Mechanism for neurotropic action of vorinostat, a pan histone deacetylase inhibitor.

1027 | Apr 24 2018

Shukla S et al. suggested that vorinostat exerts a positive effect on the neuritogenesis via activation of MEK1/2 & PI3K pathways involving an upstream kinase, TrkA. Bioactive small molecules with neurotrophic and neuritogenic actions, like vorinostat identified in the present study, hold great promise as therapeutic agents for treatment of neurodegenerative diseases and neuronal injuries by virtue of their ability to stimulate neuritic outgrowth. [Read the Full Post]

Targeting synthetic lethality between the SRC kinase and the EPHB6 receptor may benefit cancer treatment

1108 | Apr 22 2018

Paul JM et al. indicated the observations are of potential practical importance, since TNBC is an aggressive heterogeneous malignancy with a very high rate of patient mortality due to the lack of targeted therapies, and our work indicates that FDA-approved SRC inhibitors may potentially be used in a personalized manner for treating patients with EPHB6-deficient TNBC. Our findings are also of a general interest, as EPHB6 is downregulated in multiple malignancies and our data serve as a proof of principle that EPHB6 deficiency may be targeted by small molecule inhibitors in the SL approach. [Read the Full Post]

Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration

1349 | Apr 19 2018

Aras S et al. showed that binding of MNRR1 to COX is promoted by phosphorylation at tyrosine-99 and that this interaction stimulates respiration. We show that phosphorylation of MNRR1 takes place in mitochondria and is mediated by Abl2 kinase (ARG). A family with Charcot-Marie-Tooth disease type 1A with an exaggerated phenotype harbors a Q112H mutation in MNRR1, located in a domain that is necessary for transcriptional activation by MNRR1. Furthermore, the mutation causes the protein to function suboptimally in the mitochondria in response to cellular stress. The Q112H mutation hinders the ability of the protein to interact with Abl kinase, leading to defective tyrosine phosphorylation and a resultant defect in respiration. [Read the Full Post]

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455

1323 | Apr 16 2018

Wu D et al. revealed that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

0 | Apr 15 2018

Rebouissou S et al. indicated that tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis

2209 | Apr 11 2018

Shao X et al. indicated that our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy. [Read the Full Post]

Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area

1262 | Apr 10 2018

Dutton JW 3rd et al. supported the possibility that ALK might be a novel target of pharmacotherapy for reducing excessive alcohol consumption. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

3382 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors

1180 | Apr 02 2018

Martinho O et al. proposed that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients. [Read the Full Post]

Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion

696 | Apr 01 2018

Chang N et al. demonstrated that dasatinib and PKI-587 might serve as promising anticancer drug candidates for treating MIBC with combined EGFR gene amplification and PTEN deletion. [Read the Full Post]

The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition

1297 | Mar 31 2018

Mologni L et al. supported the use of combination strategies with PIM and PI3K inhibitors as effective treatment for PCa cases. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

2135 | Mar 29 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

885 | Mar 26 2018

Breitkopf SB et al. indicated a disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. [Read the Full Post]

Co-Targeting IGF-1R and Autophagy Enhances the Effects of Cell Growth Suppression and Apoptosis Induced by the IGF-1R Inhibitor NVP-AEW541 in Triple-Negative Breast Cancer Cells

799 | Mar 25 2018

Wu W et al. revealed that combined use autophagy-disrupting agents can enhance the therapeutic efficacy of IGF-1R inhibitors in TNBC cells and may provide a valuable treatment strategy for IGF-1R inhibitor-based therapies for TNBC and other IGF-1 signaling-associated tumors. [Read the Full Post]

Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma

725 | Mar 25 2018

Xu L et al. showed a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. [Read the Full Post]

Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells

1312 | Mar 18 2018

Barcus CE et al. suggested that PRL signaling to FAK and SFKs may be useful targets in clinical aggressive ERα+ breast carcinomas. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

0 | Mar 18 2018

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1

763 | Mar 03 2018

Li X et al. revealed a novel mechanism underlying the anti-metastasis function of NDGA and indicate the potential value of NDGA in NRP1 targeting therapy for selected subtypes of cancer. [Read the Full Post]

E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells

1331 | Feb 19 2018

Kato T et al. suggested that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors. [Read the Full Post]

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4

1535 | Feb 17 2018

Tian L et al. indicated Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer. [Read the Full Post]

FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop

786 | Feb 16 2018

Wang Y et al. indicate that FOXM1 promotes acquired resistance to gefitinib of lung adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a positive feedback loop to promote lung adenocarcinoma development. [Read the Full Post]

Dihydroartemisin inhibits glioma invasiveness via a ROS to P53 to β-catenin signaling

4477 | Feb 16 2018

Que Z et al. indicated that DHA inhibited the migration and invasion of human glioma cells with different types of p53 via different pathways. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

811 | Feb 15 2018

Rebouissou S et al. showed that Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

MEK2 is a prognostic marker and potential chemo-sensitizing target for glioma patients undergoing temozolomide treatment

1055 | Feb 12 2018

He H et al. indicated that the expression level of MEK2 could serve as a prognostic marker for glioma chemotherapy and that MEK2 antagonists can be used as chemo-sensitizers to enhance the treatment efficacy of TMZ. [Read the Full Post]

Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism

883 | Feb 06 2018

El Bezawy R et al. showed impressive inhibitory effects induced by miR-34a on DMPM cell proliferation, invasion, and growth in immunodeficient mice strongly suggest the potential clinical utility of a miR-34a-replacement therapy for the treatment of such a still incurable disease. On the other hand, we provide the first evidence of a potential cytoprotective/resistance mechanism that may arise towards miRNA-based therapies through the persistent activation of RTK downstream signaling. [Read the Full Post]

Development of Novel Patient-Derived Preclinical Models from Malignant Effusions in Patients with Tyrosine Kinase Inhibitor-Resistant Clear Cell Renal Cell Carcinoma

1514 | Feb 02 2018

Jang J et al. suggested that the PDC-PDX preclinical model we developed using malignant effusions can be a useful preclinical model to interrogate sensitivity to targeted agents based on genomic alterations. [Read the Full Post]

3D microtumors in vitro supported by perfused vascular networks

1865 | Feb 02 2018

Sobrino A et al. indicated that tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

0 | Feb 01 2018

Kim HK et al. considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials. [Read the Full Post]

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

1723 | Jan 24 2018

Bukong TN et al. demonstrated a novel, functional, and multicellular role for SYK phosphorylation in modulating immune cell-driven liver inflammation, hepatocyte cell death, and steatosis at different stages of ALD. [Read the Full Post]

Synthetic lethal interaction of cetuximab with MEK1/2 inhibition in NRAS-mutant metastatic colorectal cancer

927 | Jan 23 2018

Queralt B et al. showed that synthetic lethal interaction of cetuximab in combination with MEK1/2 inhibition for the NRAS mutant subgroup of mCRC underscores the importance of therapeutic intervention both in the MEK-ERK and EGFR pathways to achieve maximal therapeutic efficacy against NRAS-mutant mCRC tumors. [Read the Full Post]

Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines

832 | Jan 23 2018

Fernández ML et al. showed the greatest anti-proliferative effects. This study serves as a basis for much needed future research on MEKi drug efficacy in LGSC. [Read the Full Post]

Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

1117 | Jan 21 2018

Zhang J et al. suggested that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. [Read the Full Post]

Arsenic trioxide and all-trans-retinoic acid selectively exert synergistic cytotoxicity against FLT3-ITD AML cells via co-inhibition of FLT3 signaling pathways

1579 | Jan 13 2018

Wang LN et al. provided experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination. [Read the Full Post]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

2447 | Jan 11 2018

Pan B et al. provided new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations. [Read the Full Post]

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

1312 | Jan 06 2018

Peterse EF et al. indicated that the IGF pathway is not essential for chondrosarcoma growth, migration or chemoresistance. [Read the Full Post]

Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors

0 | Jan 02 2018

Wragg JW et al. unravel specific features of antiangiogenic resistance, with potential therapeutic implications. [Read the Full Post]

Adaptive and Acquired Resistance to EGFR Inhibitors Converge on the MAPK Pathway

1512 | Jan 01 2018

Ma P et al. demonstrated that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

0 | Dec 24 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells

1947 | Dec 24 2017

Zhang Y et al. provided novel insights into the mechanism of ErbB2 inhibition by neratinib. [Read the Full Post]

Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA-ROCK pathway

2609 | Dec 21 2017

Dasgupta SK et al. suggested that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib-induced pulmonary changes. [Read the Full Post]

Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications

2174 | Dec 16 2017

Yadav SS et al. observed that both androgen receptor (AR) positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. [Read the Full Post]

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

1947 | Dec 15 2017

Hsieh MS et al. concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. [Read the Full Post]

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

4093 | Dec 10 2017

Abraham SA et al. found that LSCs can be eradicated. [Read the Full Post]

MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer

2163 | Dec 10 2017

Nanjo S et al. suggested that combination therapy with MET inhibitors may be promising for controlling leptomeningeal carcinomatosis that acquires resistance to EGFR-TKIs [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 | Dec 06 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

1822 | Dec 06 2017

Shimada Y et al. showed that rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. [Read the Full Post]

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling

1173 | Dec 05 2017

Ji C et al. concluded that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant. [Read the Full Post]

Arsenite suppresses angiogenesis of vascular endothelial cells mediated by Platelet Derived Growth Factor Receptor-beta

1344 | Dec 03 2017

Wang X et al. concluded that arsenite suppressed the angiogenesis of the vascular endothelial cells, that this effect is mediated by PDGFR-beta, and postulate that it might contribute to the injuries of blood vessel in arsenism. [Read the Full Post]

Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans

1299 | Nov 27 2017

Fang W et al. indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis. [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

0 | Nov 21 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

An Optimized Chromatographic Strategy for Multiplexing In Parallel Reaction Monitoring Mass Spectrometry: Insights from Quantitation of Activated Kinases

1026 | Nov 20 2017

Urisman A et al. obtained from these analyses reveal compensatory activation of TGF-β family receptors as a response to MAPK blockade. The gains achieved using this label-free PRM multiplexing strategy will benefit a wide array of biological applications. [Read the Full Post]

The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats

1247 | Nov 09 2017

Yan JF et al. indicated that through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy. [Read the Full Post]

Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal Differentiation

1493 | Nov 09 2017

Wu NL et al. unraveled the role of Syk in EGFR-mediated signaling and reveals regulatory roles of Syk in keratinocyte differentiation, suggesting the clinical potential of topical or systemic Syk inhibitors in the treatment of skin diseases with aberrant differentiation. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Nov 08 2017

Simioni C et al. indicated that co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Quantitative proteomics of breast tumors: Tissue quality assessment to clinical biomarkers

2048 | Nov 06 2017

Chen Y, et al. showed that combined with biomarkers for tissue quality and histological content are implemented in a three-tier multiplexed assay platform, which is translated from cell line models into frozen tumor tissues banked from breast cancer patients. [Read the Full Post]

Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis

1886 | Nov 05 2017

Li DQ et al. showed that PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology. [Read the Full Post]

Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells

1079 | Nov 04 2017

Lu Y et al. suggested that AXL can undergo sequential processing mediated by various proteases kept in a homeostatic balance. [Read the Full Post]

IGF-II-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α in myoblast cells involves PI3K/Akt/FoxO1 signaling pathway

862 | Nov 03 2017

Mu X et al. indicated that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways. [Read the Full Post]

Hepatocyte growth factor reduces sensitivity to the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib, in lung adenocarcinoma cells harboring wild-type EGFR

30 | Nov 02 2017

Yang H et al. suggested that HGF reduced the gefitinib sensitivity through MET and downstream PI3K and MAPK pathways. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

0 | Nov 01 2017

Wang Y et al. provided a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

S100B impairs glycolysis via enhanced poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase in rodent muscle cells

1582 | Oct 30 2017

Hosokawa K et al. concluded that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. conclude that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 | Oct 25 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Novel Mechanisms for the Antifibrotic Action of Nintedanib

1961 | Oct 22 2017

Rangarajan S et al. showed that Nintedanib down-regulated protein and mRNA expression of extracellular matrix (ECM) proteins, fibronectin, and collagen 1a1 while inhibiting transforming growth factor (TGF)-β1-induced myofibroblast differentiation. Nintedanib also induced beclin-1-dependent, ATG7-independent autophagy. Nintedanib's ECM-suppressive actions were not mediated by canonical autophagy. Nintedanib inhibited early events in TGF-β signaling, specifically tyrosine phosphorylation of the type II TGF-β receptor, activation of SMAD3, and p38 mitogen-activated protein kinase. Nintedanib down-regulates ECM production and induces noncanonical autophagy in IPF fibroblasts while inhibiting TGF-β signaling. [Read the Full Post]

Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor

873 | Oct 19 2017

Davaadelger B, et al. demonstrated 1) p53 expression determines the effect of IGF-1R inhibition on cancer cell CP response, and 2) crosstalk between the IGF-1R/AKT/mTORC1 pathway and p53 and p27 can reduce cancer cell responsiveness to chemotherapy and may ultimately limit the effectiveness of IGF-1R pathway inhibitors in the clinic. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 19 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Resistance Mechanism against Trastuzumab in HER2-Positive Cancer Cells and Its Negation by Src Inhibition

1594 | Oct 16 2017

Jin MH et al. suggested that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

0 | Oct 12 2017

Saha SK et al. provided a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. [Read the Full Post]

Effects of bavachin and its regulation of melanin synthesis in A375 cells

0 | Oct 10 2017

Wang JH, et al. found that bavachin inhibited the synthesis of melanin on A375 cells by inhibiting the protein and mRNA expression of TYR, TRP-1, TRP-2, ERK1, ERK2 andJNK2. [Read the Full Post]

Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies

1735 | Oct 08 2017

Shaver TM et al. identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. [Read the Full Post]

Shh mediates PDGF-induced contractile-to-synthetic phenotypic modulation in vascular smooth muscle cells through regulation of KLF4

0 | Oct 08 2017

Zeng Q et al. provided critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4. [Read the Full Post]

MEK inhibitor CI-1040 induces apoptosis in acute myeloid leukemia cells in vitro

1012 | Oct 07 2017

Wei CR et al. demonstrated that CI-1040 induce apoptosis of U-937 cells and might be a new therapeutic option for the treatment of AML. [Read the Full Post]

Cabozantinib is selectively cytotoxic in acute myeloid leukemia cells with FLT3-internal tandem duplication (FLT3-ITD)

1639 | Oct 03 2017

Lu JW et al. showed that Clinical trials evaluating the efficacy of cabozantinib in acute myeloid leukemia (AML) with FLT3-ITD are warranted. [Read the Full Post]

In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors

1408 | Oct 03 2017

Zhao Z et al. provided a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

0 | Oct 02 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]

Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging

1237 | Sep 30 2017

Cuccarese MF et al. revealed that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

0 | Sep 27 2017

Virakul S et al. found that multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Neurotoxic reactive astrocytes are induced by activated microglia

1275 | Sep 26 2017

Liddelow SA et al. help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases. [Read the Full Post]

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis

0 | Sep 14 2017

Kobayashi K et al. suggested that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. [Read the Full Post]

IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer

1110 | Sep 01 2017

Yao C et al. defined the crucial functions of IGF/STAT3/NANOG/Slug signaling axis in the progression of CRC by operating EMT and CSCs properties, which make them served as potential therapeutic targets for treatment of CRC. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

3284 | Sep 01 2017

Simioni C et al. showed that dephosphorylation of pAkt and pS6 showed the cytotoxicity of these compounds. Either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells

1479 | Aug 31 2017

Kim HS et al. showed that GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs. [Read the Full Post]

Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

1961 | Aug 31 2017

Mizuuchi H et al. analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene. [Read the Full Post]

Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways

1111 | Aug 21 2017

Zhang L et al. showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

4103 | Aug 16 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]

Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398

1728 | Aug 15 2017

Datta J et al. suggested a role for Akt pathway in mediating acquired resistance to FGFR inhibition. [Read the Full Post]

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma

1443 | Aug 13 2017

Hanes R et al. indicated that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2. [Read the Full Post]

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression

0 | Aug 12 2017

Jones RJ et al. concluded LTP may reactivate EBV-positive resting memory B cells thereby enhancing EBV lytic cycle and host immune suppression [Read the Full Post]

ZFX Facilitates Cell Proliferation and Imatinib Resistance in Chronic Myeloid Leukemia Cells

1534 | Aug 10 2017

Jingjing Wu et al. suggested that ZFX is a novel oncogene promoting cell proliferation and inducing imatinib resistance via PI3K/Akt signaling pathway. ZFX may represent a potential therapeutic target in CML. [Read the Full Post]

TGF-β1 promotes Staphylococcus aureus adhesion to and invasion into bovine mammary fibroblasts via the ERK pathway

2624 | Aug 07 2017

Zhao S et al. indicated that TGF-β1 could promote S. aureus adhesion to and invasion into BMFBs by increasing Collagen I and α-SMA expression and may provide a novel target for controlling bovine mastitis. [Read the Full Post]

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

0 | Aug 04 2017

Hamasy A et al. identified three potential ibrutinib resistance scenarios for cysteine 481 replacement. [Read the Full Post]

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

2955 | Aug 01 2017

Appelbe OK et al. suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity. [Read the Full Post]

Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo

2844 | Aug 01 2017

Wang W et al. believe that Y-632, acting as a novel small-molecule inhibitor of the Hsp90-Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib-resistant leukemia. [Read the Full Post]

Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors

2394 | Jul 31 2017

Wragg JW et al. unraveled specific features of antiangiogenic resistance, with potential therapeutic implications. [Read the Full Post]

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model

2360 | Jul 28 2017

Omachi K et al. suggested that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2420 | Jul 28 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients. [Read the Full Post]

PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma

1822 | Jul 27 2017

Kanteti R et al. showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiting MPM tumor growth. In conclusion our findings suggest that dual inhibition of PI3K and MET pathway is an effective strategy in treating MPM as compared to a single agent. [Read the Full Post]

Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1

1923 | Jul 27 2017

Zhu K et al. suggested that EGCG has an anticancer effect on OS cells, at least partially, through regulating miR-1/c-MET interaction. [Read the Full Post]

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib

5714 | Jul 26 2017

Girgert R et al. showed that reduction of GPER expression is a promising therapeutic approach for TNBC. [Read the Full Post]

cMET inhibitor crizotinib impairs angiogenesis and reduces tumor burden in the C3(1)-Tag model of basal-like breast cancer

1943 | Jul 26 2017

Cozzo AJ et al. showed cMET inhibition by crizotinib limited tumor development and microvascular density in basal-like tumor-bearing mice but did not appear to be an effective preventive agent for BBC. [Read the Full Post]

Inhibition of the NF-κB pathway by nafamostat mesilate suppresses colorectal cancer growth and metastasis

1029 | Jul 19 2017

Lu YX et al. suggest that nafamostat mesilate, a relatively non-toxic drug that targets NF-κB and Erk, may, in combination with oxaliplatin, represent a novel therapeutic strategy for CRC treatment. [Read the Full Post]

Metalloproteinase-9 contributes to endothelial dysfunction in atherosclerosis via protease activated receptor-1

1304 | Jul 13 2017

Florence JM et al. demonstrated that metalloproteinase-9 could activate endothelial cells and induce their apoptosis via cleavage of protease activated receptor-1. In summary, better understanding of metalloproteinase-9's pathogenic capabilities as well as novel signaling pathways involved may lead to development of treatments which may provide additional benefits to atherosclerosis patients with a history of second hand smoke exposure. [Read the Full Post]

Analysis of Endogenous Protein Interactions of Polycomb Group of Proteins in Mouse Embryonic Stem Cells

0 | Jul 06 2017

Morey L et al. described several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells. [Read the Full Post]

Inhibition of acquired-resistance hepatocellular carcinoma cell growth by combining sorafenib with phosphoinositide 3-kinase and rat sarcoma inhibitor

1181 | Jul 06 2017

J Surg Res have showed that both inhibitors of PI3K/mTOR and RAS/ERK signaling are potentially effective antihepatocellular carcinoma drugs especially in treating sorafenib-resistant hepatocellular carcinoma. [Read the Full Post]

The HSP90 inhibitor, NVP-AUY922, sensitizes KRAS-mutant non-small cell lung cancer with intrinsic resistance to MEK inhibitor, trametinib

1227 | Jul 05 2017

Park KS et al. showed that intrinsic resistance to MEK inhibition occurred via high AKT expression by PI3K activation as a bypass pathway. The HSP90 inhibitor AUY922 suppressed PI3K-AKT-mTOR and RAF-MEK-ERK, and rendered cells sensitive to trametinib (GSK1120212). Synergy from the combination of the two drugs was observed in only sub-therapeutic concentrations of either drug. Dual inhibition of the HSP90 and MEK signaling pathways with sub-therapeutic doses may represent a potent therapeutic strategy to treat KRAS-mutant NSCLC with intrinsic resistance to MEK inhibition and to resolve the toxicity observed upon dual inhibition of AKT and MEK at therapeutic doses in clinical trials. [Read the Full Post]

MET Inhibition in Clear Cell Renal Cell Carcinoma

0 | Jul 01 2017

Xie Z et al. provided further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2798 | Jun 29 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

3724 | Jun 27 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

A PGC1α-mediated transcriptional axis suppresses melanoma metastasis

2995 | Jun 23 2017

Luo C et al. revealed that PGC1α maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. [Read the Full Post]

Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin.

1177 | Jun 20 2017

Li W et al. revealed a regulatory role for HIF-1α in VM and suggests that targeting either HIF-1α or EMT may be a valuable strategy for the elimination of CRC metastasis. [Read the Full Post]

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

1671 | Jun 17 2017

Zhao B, et al. identified new strategies to treat dynamic tumor vulnerabilities. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

2881 | Jun 16 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Functionalized gold nanoparticles improve afatinib delivery into cancer cells

2727 | Jun 16 2017

Coelho SC et al. found that PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

5939 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk

2128 | Jun 11 2017

Peng M, et al. found these two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation. [Read the Full Post]

The new and recurrent FLT3 juxtamembrane deletion mutation shows a dominant negative effect on the wild-type FLT3 receptor

1766 | May 31 2017

Sandhöfer N et al. that FLT3 p.Q569Vfs*2 is the first FLT3 mutation with a dominant negative effect on the WT receptor. [Read the Full Post]

Interferon-Gamma and Fas Are Involved in Porphyromonas gingivalis-Induced Apoptosis of Human Extravillous Trophoblast-Derived HTR8/SVneo Cells via Extracellular Signal-Regulated Kinase 1/2 Pathway

1497 | May 30 2017

Ren H et al. demonstrated Pg induces IFN-γ secretion, Fas expression, and apoptosis in human extravillous trophoblast-derived HTR8/SVneo cells in an ERK1/2-dependent manner, and IFN-γ (explored by recombinant IFN-γ) and Fas are involved in Pg-induced apoptosis. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

0 | May 28 2017

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

1892 | May 28 2017

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

2431 | May 22 2017

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters [Read the Full Post]

FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling

1819 | May 21 2017

Daly C, et al. found that FGFR3-TACC3 fusion proteins may represent a novel mechanism of acquired resistance in EGFR-dependent cancers of multiple cell lineages. [Read the Full Post]

Additive effects of low concentrations of estradiol-17β and progesterone on nitric oxide production by human vascular endothelial cells through shared signaling pathways

1320 | May 21 2017

Pang Y et al. suggested that low doses of E2 and P4 may also have some beneficial cardiovascular effects in vivo when administered as hormone replacement therapy (HRT) for post-menopausal women. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells.

0 | May 18 2017

Khan IA et al. have identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

3767 | May 17 2017

Miller RE et al. suggested that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. [Read the Full Post]

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

0 | May 16 2017

Sun H et al. showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

3432 | May 15 2017

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

0 | May 14 2017

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo

2417 | May 12 2017

Dey J et al. found a platform for rapid, quantitative assessment of multiple drug combinations simultaneously in solid tumors In vivo. [Read the Full Post]

Src as a Therapeutic Target in Biliary Tract Cancer.

0 | May 11 2017

Nam AR et al. suggested that Src might be a potential therapeutic target in BTC. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 09 2017

Saafan H et al.found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 08 2017

Saafan H et al. found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.

4282 | May 07 2017

Shimada T et al suggested that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling. Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

0 | May 07 2017

Scheipl S et al provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

0 | May 06 2017

Song S et al. identified a novel mechanism to reveal the formation of EndoMT in PAH, and implied that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [Read the Full Post]

MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models

1704 | May 03 2017

Wang K et al demonstrated the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors. [Read the Full Post]

The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

1679 | Apr 29 2017

Song S et al. identified a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [Read the Full Post]

Depletion of FOXM1 via MET Targeting Underlies Establishment of a DNA Damage-Induced Senescence Program in Gastric Cancer

0 | Apr 26 2017

Francica P et al. suggested that FOXM1 has been identified as a key downstream effector and potential clinical biomarker that mediates MET signaling following infliction of DNA damage in gastric tumors. [Read the Full Post]

MAP3K19-Is-a-Novel-Regulator-of-TGF-B-Signaling-That-Impacts-Bleomycin-Induced-Lung-Injury-and-Pulmonary-Fibrosis

8803 | Apr 23 2017

Boehme SA et al suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

Lassa virus cell entry via dystroglycan involves an unusual pathway of macropinocytosis.

0 | Apr 23 2017

Oppliger J et al revealed that DG can link LASV to an unusual pathway of macropinocytosis that causes only minimal perturbation of the host cell and identifies cellular kinases to be possible novel targets for therapeutic intervention. [Read the Full Post]

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

0 | Apr 20 2017

Habata S et al. suggested that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. [Read the Full Post]

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

1804 | Apr 15 2017

Cidre-Aranaz F et al. suggested that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

7347 | Apr 09 2017

Collectively, Wu C et al revealed, for the first time, a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells

1619 | Apr 07 2017

Abe M et al. found that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression. [Read the Full Post]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

1901 | Apr 05 2017

Tsimafeyeu I et al showed that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

2974 | Apr 03 2017

Huang A et al revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

iRGD-Decorated Polymeric Nanoparticles for the Efficient Delivery of Vandetanib to Hepatocellular Carcinoma: Preparation and in Vitro and in Vivo Evaluation

1607 | Apr 01 2017

Wang J et al. demonstrated that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves the potency of currently available, orally delivered agents. [Read the Full Post]

Small-Molecule Induction of Canine Embryonic Stem Cells Toward Naïve Pluripotency

1156 | Mar 25 2017

Tobias IC et al. suggested that 2iL culture conditions promote the conversion of cESCs toward an epigenetically distinct pluripotent state resembling naïve PSCs. [Read the Full Post]

Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

1967 | Mar 22 2017

Duckworth C et al suggestec that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. [Read the Full Post]

Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma

0 | Mar 21 2017

Xiang Q et al suggested that the potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status. [Read the Full Post]

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

0 | Mar 15 2017

Ceccon M et al. found the knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Mar 13 2017

Sampson VB et al suggested that potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization

0 | Mar 12 2017

Lin YC et al found that the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases. [Read the Full Post]

Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling

0 | Mar 12 2017

Kistowska M et al identified Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process. [Read the Full Post]

GRP78 confers the resistance to 5-FU by activating the c-Src/LSF/TS Axis in hepatocellular carcinoma

1896 | Mar 11 2017

Gu YJ, et al. further identified that GRP78 interacts physically with c-Src through its ATPase domain and promotes the phosphorylation of c-Src, which in turn increases the expression of LSF in the nucleus. Together, GRP78 confers the resistance to 5-FU by up-regulating the c-Src/LSF/TS axis via its ATPase domain. [Read the Full Post]

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

0 | Mar 11 2017

Chihara K et al. suggested that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. [Read the Full Post]

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

0 | Mar 11 2017

Angata T et al found that Siglec-14 and its downstream signaling pathway facilitate the "infection-inflammation-exacerbation" axis of COPD disease progression, and may represent promising targets for therapeutic intervention. [Read the Full Post]

Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway

0 | Mar 08 2017

Ying R et al. revealed that H2S could protect against ER stress-induced EndMT through Src pathway, which may be a novel role for the cardioprotection of H2S. [Read the Full Post]

Insulin-like growth factor I promotes oocyte maturation through increasing the expression and phosphorylation of epidermal growth factor receptor in the zebrafish ovary

0 | Mar 04 2017

Xie L et al. lighted on the cross-talk between two important growth factors in the zebrafish ovary and the mechanism underlying the IGF-I induction on oocyte maturation. [Read the Full Post]

Targeting Non-Small Cell Lung Cancer Cells by Dual Inhibition of the Insulin Receptor and the Insulin-Like Growth Factor-1 Receptor

0 | Mar 02 2017

Vincent EE et al. concluded that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer

0 | Feb 17 2017

Manteghi S et al. establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy

0 | Feb 16 2017

Polak A et al. demonstrated that modulation of MEK/ERK pathway is an attractive therapeutic strategy overcoming GC resistance in B-ALL patients. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

2135 | Feb 08 2017

This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

3034 | Feb 06 2017

Kim TM, et al.'s result shows that Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2676 | Feb 05 2017

Kobayashi Y, et al.’‘s result shows that’Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells.

0 | Feb 05 2017

Ishibashi T, et al.'s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/ Mammalian Target of Rapamycin (mTOR) Axis is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

1977 | Feb 04 2017

Makinoshima H, et al.‘s results suggest that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma

1497 | Jan 24 2017

Xiang Q, et al.'s conclusion shows that the potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status. [Read the Full Post]

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

3841 | Jan 23 2017

Ceccon M, et al.'s knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling

1503 | Jan 20 2017

Kistowska M, et al.'s results identify Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process. [Read the Full Post]

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

1618 | Jan 19 2017

Angata T, et al. found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the "infection-inflammation-exacerbation" axis of COPD disease progression, and may represent promising targets for therapeutic intervention. [Read the Full Post]

Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization

1453 | Jan 19 2017

Lin YC, et al.'s results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases. [Read the Full Post]

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

1453 | Jan 18 2017

Chihara K, et al.'s data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. [Read the Full Post]

Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor

2258 | Jan 16 2017

Vincent EE et al. concluded that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

1855 | Jan 03 2017

The study of Mol Oncol's warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

2064 | Jan 02 2017

Makinoshima H et al. suggested that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2511 | Jan 02 2017

Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

3272 | Dec 30 2016

Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells

2858 | Dec 29 2016

Ishibashi T, et al.‘’s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

MET Inhibition in Clear Cell Renal Cell Carcinoma

2489 | Dec 23 2016

Xie Z et al. provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. [Read the Full Post]

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

2151 | Dec 17 2016

Bukong TN et al. demonstrated a novel, functional, and multicellular role for SYK phosphorylation in modulating immune cell-driven liver inflammation, hepatocyte cell death, and steatosis at different stages of ALD. [Read the Full Post]

Reconstructing the temporal progression of HIV-1 immune response pathways

2873 | Dec 13 2016

Jain S et al. experimentally validated several of TimePaths' predictions highlighting the usefulness of temporal models. [Read the Full Post]

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

1669 | Dec 11 2016

Hamasy A et al. identified three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. [Read the Full Post]

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis

3077 | Dec 02 2016

Kobayashi K et al. suggested that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

5677 | Nov 26 2016

Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies

2722 | Nov 21 2016

Shaver TM et al. identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. [Read the Full Post]

MEK inhibitor CI-1040 induces apoptosis in acute myeloid leukemia cells in vitro

1443 | Nov 21 2016

Wei CR et al. demonstrated that CI-1040 induce apoptosis of U-937 cells and might be a new therapeutic option for the treatment of AML. [Read the Full Post]

Shh mediates PDGF-induced contractile-to-synthetic phenotypic modulation in vascular smooth muscle cells through regulation of KLF4

1494 | Nov 20 2016

Zeng Q et al. provided critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4. [Read the Full Post]

Effects of bavachin and its regulation of melanin synthesis in A375 cells

1634 | Nov 18 2016

Bavachin inhibited the synthesis of melanin on A375 cells by inhibiting the protein and mRNA expression of TYR, TRP-1, TRP-2, ERK1, ERK2 andJNK2. [Read the Full Post]

The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer

1667 | Nov 18 2016

Beadnell TC et al. demonstrated that up-front combined inhibition with dasatinib and MEK1/2 or ERK1/2 inhibitors drives synergistic inhibition of growth and induction of apoptosis, indicating that combined inhibition may overcome mechanisms of survival in response to single-agent inhibition. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

4540 | Nov 16 2016

Saha SK et al. showed that IDHm ICC cells have a unique dependency on SRC and suggested that dasatinib may have therapeutic benefit against IDHm ICC. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

2268 | Nov 09 2016

Wang Y et al. provides a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer.

3161 | Nov 08 2016

Manteghi S, et al.found that we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy.

1595 | Nov 07 2016

Polak A, et al found that the data demonstrate that modulation of MEK/ERK pathway is an attractive therapeutic strategy overcoming GC resistance in B-ALL patients. [Read the Full Post]

Depletion of FOXM1 via MET Targeting Underlies Establishment of a DNA Damage-Induced Senescence Program in Gastric Cancer

1631 | Oct 31 2016

FOXM1, a negative regulator of senescence, has been identified as a key downstream effector and potential clinical biomarker that mediates MET signaling following infliction of DNA damage in gastric tumors. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

2796 | Oct 25 2016

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

2003 | Oct 25 2016

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

3189 | Oct 19 2016

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells

3338 | Oct 14 2016

Khan IA et al. identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

3400 | Oct 14 2016

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

4318 | Oct 13 2016

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

2264 | Oct 11 2016

Habata S et al. suggested that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. [Read the Full Post]

Src as a Therapeutic Target in Biliary Tract Cancer

2202 | Oct 10 2016

Nam AR et al. suggested that Src might be a potential therapeutic target in BTC. [Read the Full Post]

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

2758 | Oct 10 2016

Sun H et al. showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds and performed much better than Autodock, suggesting that the proposed strategy is a powerful tool in structure-based virtual screening. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach

2875 | Oct 08 2016

Saafan H et al. identified that differential proteins in the EGFR interactome of HCC4006rERLO0.5 cells could be related to multiple resistance mechanisms including alterations in growth factor receptor expression, cellular remodelling processes suggesting epithelial-to-mesenchymal transition as well as alterations in downstream signalling. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

3176 | Sep 30 2016

Scheipl S et al. provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling

2619 | Sep 29 2016

Shimada T, et al. revealed the molecular mechanism underlying mossy fiber sprouting. [Read the Full Post]

Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis

2700 | Sep 22 2016

Oppliger J et al. revealed novel fundamental aspects of the LASV-host cell interaction and highlights a possible candidate drug target for therapeutic intervention. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

3461 | Sep 12 2016

Wu C et al. revealed that a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

0 | Sep 08 2016

Huang A, et al. revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

2133 | Sep 08 2016

Tsimafeyeu I, et al. found that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway

2040 | Sep 02 2016

Ying R, et al. revealed that H2S could protect against ER stress-induced EndMT through Src pathway, which may be a novel role for the cardioprotection of H2S. [Read the Full Post]