Cytoskeletal Alterations that Confer Resistance to Anti-tubulin Chemotherapeutics

Arun      Kanakkanthara; Paul      H. Teesdale-Spittle; John      H. Miller

Abstract

Drugs that target microtubules are a successful class of anti-cancer agents that have been in clinical use for over two decades. Acquired resistance to these drugs, however, remains a serious problem. Microtubule alterations, such as tubulin mutations and altered β- tubulin isotype expression, are prominent factors in development of resistance. Changes in actin and intermediate filament proteins can also mediate sensitivity to microtubule-targeting drugs. This review focuses on the mechanisms by which alterations in cytoskeletal proteins lead to drug resistance. This information will be helpful for improving the targeting of microtubule toxins.

Keywords: Actin, Cytoskeleton, Drug resistance, Intermediate filament, MDR, Microtubule, Microtubule-targeting drugs, C-terminal amino acids, Microfilaments, microtubule-destabilizers