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.


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

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