Novel Drugs Targeting Microtubules: the Role of Epothilones

Gabriella      Ferrandina; Marisa      Mariani; Mirko      Andreoli; Shohreh      Shahabi; Giovanni      Scambia; Cristiano      Ferlini

doi:10.2174/138161212800626238

Abstract

Among the drugs targeting microtubule functions by interfering with tubulin subunits, epothilones represent a class of anticancer agents which recently entered clinical development. Although epothilones share mechanisms of action similar to taxanes, they have non-overlapping mechanisms of resistance; in particular, while overexpression of class III β-tubulin plays a major role in taxane resistance, epothilones display their highest efficacy in class III β-tubulin overexpressing malignancies. Three compounds belonging to this family (patupilone, ixabepilone and sagopilone), have been actively investigated in clinical trials, and some of them are at an advanced stage of development.

This review provides a comprehensive analysis of the available literature on epothilones, focusing on their clinical development and potential as an additional weapon in the arsenal against tumors.

Keywords: Epothilones, cytoskeleton, class III β-tubulin, cell survival, ovarian cancer, anticancer agents, taxane resistance, tumors, p-glycoprotein, microtubule