Microtubule stabilising agents for cancer chemotherapy

Abstract

Background: Microtubules are very important targets for cancer chemotherapy. During the past 15 years, three structurally diverse classes of microtubule stabilising agents (MSAs), namely, taxanes, epothilones and discodermolides, have been approved as anticancer agents or subjected to clinical trials, and many novel MSAs have also been identified. Objective: This review focuses on recent advances in the use of taxanes, epothilones and discodermolides, as well as some recently described natural product based MSAs. Methods: Data were identified through the search of PubMed for research articles and reviews, the website of European patents (http://ep.espacenet.com) and US patents (www.uspto.gov) for patents up to October 2008. Only well-established MSAs are mentioned in this review. Results/conclusion: Great advances have been made in the application of MSAs in antitumour clinical practice and drug discovery. Many structure–activity relationship studies of MSAs as novel anticancer drugs have been conducted in recent years. To enhance the efficacy of MSAs as clinically useful therapeutics, numerous efforts have been made in combination chemotherapy regimens and include: i) the combination of structurally different MSAs, ii) combination of MSAs with other classes of anticancer agent with a different mechanism of action and iii) novel ways of administrating well-established MSAs.

Keywords::

• anticancer
• chemotherapy
• discodermolide
• epothilone
• microtubule stabilising agent
• taxane

Acknowledgments

We thank JF Díaz of CIB, CSIC for critical reading of our manuscript, and J-z Shi for assistance in drawing chemical structures.

Notes