New microtubule-inhibiting anticancer agents

Abstract

Importance of this field: Microtubule-inhibiting drugs are among the most commonly prescribed agents in the combat against cancer, though the clinical use of these drugs is limited by acquired resistance, risk of hypersensitivity reactions and intolerable toxicity. With progress in our understanding of cytoskeleton structure and its related signaling pathways, a number of new microtubule-inhibiting agents with diversified structures and modes of action haveemerged.

What the reader will gain: This review mainly describes new microtubule-targeting anticancer agents that have been discovered (especially over the past 2 years), with emphasis on their diversity of structures and distinct modes ofaction.

Areas covered in this review: Data were obtained exclusively from public sources, including journals and scientific meeting abstracts, up to September 2009.

Take home message: A number of new agents have been discovered, and some have entered clinical trials. Even though most of these agents stabilize or destabilize tubulin via binding on the recognized tubulin binding sites, a few compounds bind to tubulin on undefined sites or interrupt microtubule in diverse ways. Moreover, some agents target microtubule indirectly such that they alter the post-translational modification of tubulin. Further investigation into their mechanism of action and evaluation of their anticancer efficacy will help to develop novel regimens that are superior to existingapproaches.

Keywords::

• anticancer
• microtubule
• preclinical
• tubulin