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Clin Cancer Res. 2015 Jun 1;21(11):2445-52. doi: 10.1158/1078-0432.CCR-14-3252. Epub 2015 Apr 2.

Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent.

Author information

1
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
2
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
3
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas Mooberry@uthscsa.edu.

Abstract

Eribulin mesylate (eribulin), an analogue of the marine natural product halichondrin B, is a microtubule-depolymerizing drug that has utility in the treatment of patients with breast cancer. Clinical trial results have demonstrated that eribulin treatment provides a survival advantage to patients with metastatic or locally advanced breast cancer previously treated with an anthracycline and a taxane. Furthermore, a pooled analysis of two pivotal phase III trials has demonstrated that eribulin also improves overall survival in several patient subgroups, including in women with HER2-negative disease and triple-negative breast cancer. This review covers the preclinical research that led to the clinical testing and approval of eribulin, as well as subsequent research that was prompted by distinct and unexpected effects of eribulin in the clinic. Initial studies with halichondrin B demonstrated unique effects on tubulin binding that resulted in distinct microtubule-dependent events and antitumor actions. Consistent with the actions of the natural product, eribulin has potent microtubule-depolymerizing activities and properties that distinguish it from other microtubule-targeting agents. Here, we review new results that further differentiate the effects of eribulin from other agents on peripheral nerves, angiogenesis, vascular remodeling, and epithelial-to-mesenchymal transition. Together, these data highlight the distinct properties of eribulin and begin to delineate the mechanisms behind the increased survival benefit provided by eribulin for patients.

PMID:
25838395
PMCID:
PMC4812567
DOI:
10.1158/1078-0432.CCR-14-3252
[Indexed for MEDLINE]
Free PMC Article

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