Microtubule-Stabilizing Natural Products as Promising Cancer Therapeutics

Brian   M.   Gallagher Jr.

doi:10.2174/092986707782794014

Abstract

Paclitaxel and related taxanes exhibit their anticancer activity by promoting tubulin polymerization and stabilizing microtubules, which results in mitotic G2/M arrest and apoptosis. The clinical success of paclitaxel in treating a wide array of tumor types has led to numerous efforts to identify novel natural products with paclitaxel-like mechanisms of action, but which may overcome some of the liabilities of the taxanes. Although the list of natural products that share the paclitaxel-like mechanism is relatively small, it continues to expand and currently includes a number of structurally distinct classes. Despite the mechanistic similarities between these classes, differences exist which may translate into their differential efficacy in the clinic. The past several years have seen a considerable amount of pre-clinical and clinical progress in developing these novel microtubule-stabilizing natural products as cancer therapeutics. This review focuses primarily on recent advances published since 2002.

Keywords: Microtubule-stabilizing, natural product, epothilone, discodermolide, laulimalide, anticancer, antitumor, paclitaxel