Title:Cytoskeletal Alterations that Confer Resistance to Anti-tubulin Chemotherapeutics
VOLUME: 13 ISSUE: 1
Author(s):Arun Kanakkanthara, Paul H. Teesdale-Spittle and John H. Miller
Affiliation:Centre for Biodiscovery and School of Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington 6140, New Zealand.
Keywords:Actin, Cytoskeleton, Drug resistance, Intermediate filament, MDR, Microtubule, Microtubule-targeting drugs, C-terminal amino acids, Microfilaments, microtubule-destabilizers
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.