Microtubules and resistance to tubulin-binding agents

Abstract

Microtubules are dynamic structures composed of α-Β-tubulin heterodimers that are essential in cell division and are important targets for cancer drugs. Mutations in Β-tubulin that affect microtubule polymer mass and/or drug binding are associated with resistance to tubulin-binding agents such as paclitaxel. The aberrant expression of specific Β-tubulin isotypes, in particular ΒIII-tubulin, or of microtubule-regulating proteins is important clinically in tumour aggressiveness and resistance to chemotherapy. In addition, changes in actin regulation can also mediate resistance to tubulin-binding agents. Understanding the molecular mechanisms that mediate resistance to tubulin-binding agents will be vital to improve the efficacy of these agents. © 2010 Macmillan Publishers Limited. All rights reserved.