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The Epothilones: Translating from the Laboratory to the Clinic

Authors' Affiliations: ¹ Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut and ² Washington Cancer Institute, Washington Hospital Center, Washington, District of Columbia

Requests for reprints: Sandra M. Swain, Washington Cancer Institute, Washington Hospital Center, 110 Irving Street Northwest, Washington, DC 20010. Phone: 202-877-8112; E-mail: sandra.m.swain{at}medstar.net.

Abstract

The epothilones are macrolide compounds that have been shown to stabilize microtubules. The epothilones are strong promoters of tubulin polymerization in vitro and have significant antitumor activity against human cancer cells that are taxane resistant, express the multidrug resistance gene MDR-1 (ABCB1), and have acquired tubulin mutations. Several epothilones have been evaluated in clinical trials in a variety of tumor types. Ixabepilone (aza-epothilone B) has significant antitumor activity in breast cancer resistant to an anthracycline and a taxane, and has been approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic or locally advanced breast cancer. There have been sustained efforts to develop pharmacodynamic markers to monitor the pharmacologic effect of the epothilones on tumors and normal tissues. The development of predictive markers for epothilone chemotherapy is highly desired to provide more tailored therapy for patients with cancer.

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