Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance.
Microtubules are important cellular targets for anticancer therapy because of their key role in mitosis. Microtubule inhibitors (MTI) such as taxanes, vinca alkaloids, and epothilones stabilize or destabilize microtubules, thereby suppressing microtubule dynamics required for proper mitotic function, effectively blocking cell cycle progression and resulting in apoptosis. In spite of their antitumor activity, innate or acquired drug resistance to MTIs such as the taxanes is common, limiting their overall clinical efficacy. Further insight into the mechanisms of action of microtubule-targeting drugs has lead to the discovery of novel agents that may provide higher efficacy with limited toxicity and help overcome resistance to conventional MTIs. This review will focus on the different mechanisms of action of MTIs, potential factors related to resistance and tolerability, and will discuss the recent approval as well as the development of new antineoplastic agents.
Perez
Edith A
EA
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL32224, USA. perez.edith@mayo.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology; D050257:Tubulin Modulators / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014748:Vinca Alkaloids / Q000494:pharmacology
D000970:Antineoplastic Agents; D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; D014748:Vinca Alkaloids