Taxol®: The First Microtubule Stabilizing Agent

Taxol((R)), an antitumor drug with significant activity, is the first microtubule stabilizing agent described in the literature. This short review of the mechanism of action of Taxol((R)) emphasizes the research done in the Horwitz' laboratory. It discusses the contribution of photoaffinity labeled analogues of Taxol((R)) toward our understanding of the binding site of the drug on the microtubule. The importance of hydrogen/deuterium exchange experiments to further our insights into the stabilization of microtubules by Taxol((R)) is addressed. The development of drug resistance, a major problem that arises in the clinic, is discussed. Studies describing differential drug binding to distinct -tubulin isotypes are presented. Looking forward, it is suggested that the -tubulin isotype content of a tumor may influence its responses to Taxol((R)).