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.