How Do Microtubule-Targeted Drugs Work? An Overview

Mary   Ann   Jordan; Kathy      Kamath

Abstract

The importance of microtubules in mitosis makes them a superb target for a group of highly successful, chemically diverse anticancer drugs. Knowledge of the mechanistic differences among the many drugs of this class is vital to understanding their tissue and cell specificity, the development of resistance, the design of novel improved drugs, optimal scheduling of treatment, and potential synergistic combinations. This overview covers microtubule assembly dynamics, the exquisite regulation of microtubule dynamics in cells by endogenous regulators, the important role of microtubule dynamics in mitosis, the diversity and number of microtubule-targeted drugs undergoing clinical development, the antimitotic mechanisms of microtubule-targeted drugs with emphasis on suppression of microtubule dynamics by vinblastine and taxol, the role of drug uptake and retention in the efficacy of microtubule-targeted drugs, and the anti-angiogenic and vascular-disrupting mechanisms of microtubule targeted drugs. In view of the success of this class of drugs, it has been argued that microtubules represent the single best cancer target identified to date, and it seems likely that drugs in this class will continue to remain an important chemotherapeutic class of drugs even as more selective chemotherapeutic approaches are developed.

Keywords: Microtubules, mitosis, cancer, drugs, tubulin, taxol, vinblastine, dynamic instability