Cytoskeletal Alterations That Confer Resistance to Anti-Tubulin Chemotherapeutics
Arun Kanakkanthara, Paul H. Teesdale-Spittle and John H. Miller
AbstractDrugs 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 ?-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.
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