Drugs that target dynamic microtubules: a new molecular perspective

Exquisite spatiotemporal regulation of microtubule dynamicity dictates cell division, a process by which a parent cell divides into two daughters. Panels show confocal immunomicrographs of HeLa cells with microtubules (green) and DNA (red) displaying hallmarks of a typical cell division process.

Author: Stanton, R.A.; Gernert, K.M.; Nettles, J.H.; Aneja, R.

Description: Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.

Subject headings: Animals; Antineoplastic Agents/chemistry/pharmacology; Humans; Microtubules/drug effects/metabolism; Pharmaceutical Preparations/chemistry/metabolism; Cancer

Publication year: 2011

Journal or book title: Medicinal Research Reviews

Volume: 31

Issue: 3

Pages: 443-481

Find the full text: https://www.strategian.com/fulltext/Stanton2011.pdf

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Type: Journal Article

Serial number: 1263