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Epothilones: Mechanism of Action and Biologic Activity

From the Department of Medicine, Department of Pharmacology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School; and The Cancer Institute of New Jersey, New Brunswick, NJ.

Address reprint requests to Eric H. Rubin, MD, The Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ 08901; e-mail: ehrubin{at}umdnj.edu

Drugs that target microtubules are among the most commonly prescribed anticancer therapies. Although the mechanisms by which perturbation of microtubule function leads to selective death of cancer cells remain unclear, several new microtubule-targeting compounds are undergoing clinical testing. In part, these efforts focus on overcoming some of the problems associated with taxane-based therapies, including formulation and administration difficulties and susceptibility to resistance conferred by P-glycoprotein. Epothilones have emerged from these efforts as a promising new class of anticancer drugs. Preclinical studies indicate that epothilones bind to and stabilize microtubules in a manner similar but not identical to that of paclitaxel and that epothilones are effective in paclitaxel-resistant tumor models. Clinical phase I and early phase II data are available for BMS-247550, BMS-310705, EPO906, and KOS-862. The results suggest that these compounds have a broad range of antitumor activity at doses and schedules associated with tolerable side effects.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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