Home Blog of Signal Transduction Neuronal Signaling P-gp Two strategies to overcome eribulin resistance: pharmacokinetic imaging and nanoparticle delivery system

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Two strategies to overcome eribulin resistance: pharmacokinetic imaging and nanoparticle delivery system

 

Eribulin mesylate (Halaven) is an emerging therapy for metastatic breast cancer and is followed by taxane or anthracycline. The combinational treatment led to increased median of overall survival. However, the performance of eribulin was not satisfactory when assessed by an independent review, the reason was unclear. To investigate the resistance mechanism, Laughney et al. developed a fluorescent eribulin analog, which has similar characteristics with eribulin in pharmacokinetic (PK) properties and cytotoxic activity. The article was published on Science Translational Medicine, recently.

 

Previously studies showed multidrug resistance protein 1 (MDR1) is a key factor that mediate the increase of drug efflux in cell culture. By using fluorescent eribulin analog, researchers  investigated the in vivo cellular accumulation of the drug in heterogeneous tumors, then found the resistance to eribulin depended directly on MDR1. Furthermore, they showed the third-generation MDR1 inhibitor encapsulated within a nanoparticle delivery system can rescue drug accumulation, reduce multidrug-resistant, and enhance the eribulin effect in mice. The nanoparticle system solved the problem of inefficient inhibitor delivery to the tumor. The study demonstrates a strategy of PK for to reveal drug-resistant mechanisms, and a strategy of nanoparticle system to overcome the resistance.

 

Reference:
Sci Transl Med. 2014 Nov 5;6(261):261ra152

Related Products

Cat.No. Product Name Information
S1026 Imatinib Mesylate Imatinib Mesylate is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. Imatinib Mesylate (STI571) induces autophagy.
S1490 Ponatinib Ponatinib is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy.

Related Targets

P-gp