New microtubule-inhibiting anticancer agents.
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 have emerged.


RESULTS
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 of action.


METHODS
Data were obtained exclusively from public sources, including journals and scientific meeting abstracts, up to September 2009.


CONCLUSIONS
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 existing approaches.
Chen
Si-Meng
SM
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China.
Meng
Ling-Hua
LH
Ding
Jian
J
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents