Blog of Signaling Pathways

Entinostat for the treatment of breast cancer

790 views | Sep 20 2019

Trapani D et a. offered the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines. [Read the Full Post]

Acetazolamide potentiates the anti-tumor potential of HDACi, MS-275, in neuroblastoma

767 views | Sep 20 2019

Bayat Mokhtari R et al. indicated the significant reduction in initial tumorigenicity and subsequent abrogation upon serial xenografting suggests potential elimination of the NB CSC fraction. The significant potentiation of MS-275 by AZ is a promising therapeutic approach and one amenable for administration to patients given their current clinical utility. [Read the Full Post]

Copanlisib: An Intravenous Phosphatidylinositol 3-Kinase (PI3K) Inhibitor for the Treatment of Relapsed Follicular Lymphoma

0 views | Sep 19 2019

Eltantawy A et al. provided an alternative option for patients with relapsed FL. It is safe and effective and has an acceptable toxicity profile. [Read the Full Post]

Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine

332 views | Sep 18 2019

Gelbert LM et al. identified a potent, orally active small-molecule inhibitor of CDK4/6 that is active in xenograft tumors. LY2835219is currently in clinical development. [Read the Full Post]

Copanlisib: First Global Approval

0 views | Sep 18 2019

Markham A summarizes the milestones in the development of copanlisib leading to this first approval for relapsed follicular lymphoma. [Read the Full Post]

The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia

293 views | Sep 16 2019

Hoellenriegel J et al. provided an explanation for the clinical activity of CAL-101, and a roadmap for future therapeutic development. [Read the Full Post]

GS-1101: a delta-specific PI3K inhibitor in chronic lymphocytic leukemia

343 views | Sep 16 2019

Macias-Perez IM et al. indicated this article will review new insights into the pathophysiology of CLL, the preclinical rationale of a PI3Kδ inhibitor in CLL, and the clinical evidence supporting this first-in-class therapeutic target for CLL patients. [Read the Full Post]

Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth

587 views | 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 views | 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]

LBH589 Inhibits Glioblastoma Growth and Angiogenesis Through Suppression of HIF-1α Expression

2110 views | Sep 14 2019

Yao ZG et al. supports the role of HDAC inhibitors as a therapeutic strategy to target tumor angiogenesis. [Read the Full Post]

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia

528 views | 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]

Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation

504 views | Sep 12 2019

Fokas E et al. support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. [Read the Full Post]

Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury

501 views | Sep 11 2019

Slavin SA et al. indicated these data imply a role of autophagy in lung vascular injury and reveal the protective and therapeutic utility of 3-MA against ALI. [Read the Full Post]

Synthesis and screening of 3-MA derivatives for autophagy inhibitors

517 views | Sep 11 2019

Wu Y et al. demonstrated that chemical modification of an existing autophagy inhibitor is an effective method to generate improved autophagy inhibitors. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

839 views | Sep 09 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

796 views | Sep 09 2019

Sun QY et al. revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling. [Read the Full Post]

Activation of Wnt signaling promotes olaparib resistant ovarian cancer

605 views | Sep 08 2019

Yamamoto TM et al. demonstrated that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARP and Wnt inhibitors. [Read the Full Post]

Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer

542 views | Sep 08 2019

Dockery LE et al. indicated this article reviews the mechanisms of action, safety, approval, and indications for use of the PARP inhibitor rucaparib as well as future trials and use of rucaparib's companion diagnostic test. [Read the Full Post]

BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma

943 views | Sep 07 2019

Gobin B et al. indicated the present work shows that BYL719 is a promising drug in either a single or multidrug approach to curing bone sarcoma. [Read the Full Post]

Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion

488 views | Sep 07 2019

Mauvezin C et al. identified the ER-calcium ATPase Ca-P60A/dSERCA as a novel target of bafilomycin A1. Autophagosome-lysosome fusion was defective in Ca-P60A/dSERCA-depleted cells, and bafilomycin A1 induced a significant increase in cytosolic calcium concentration and disrupted Ca-P60A/SERCA-mediated fusion. Thus, bafilomycin A1 disrupts autophagic flux by independently inhibiting V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. [Read the Full Post]

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