Microtubule-Stabilizing Natural Products as Promising Cancer Therapeutics

Brian   M.   Gallagher Jr.

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