Microtubule destabilising agents: far more than just antimitotic anticancer drugs

Br J Clin Pharmacol. 2017 Feb;83(2):255-268. doi: 10.1111/bcp.13126. Epub 2016 Oct 18.

Abstract

Vinca alkaloids have been approved as anticancer drugs for more than 50 years. They have been classified as cytotoxic chemotherapy drugs that act during cellular mitosis, enabling them to target fast growing cancer cells. With the evolution of cancer drug development there has been a shift towards new "targeted" therapies to avoid the side effects and general toxicities of "cytotoxic chemotherapies" such as the vinca alkaloids. Due to their original classification, many have overlooked the fact that vinca alkaloids, taxanes and related drugs do have a specific molecular target: tubulin. They continue to be some of the most effective anticancer drugs, perhaps because their actions upon the microtubule network extend far beyond the ability to halt cells in mitosis, and include the induction of apoptosis at all phases of the cell cycle. In this review, we highlight the numerous cellular consequences of disrupting microtubule dynamics, expanding the textbook knowledge of microtubule destabilising agents and providing novel opportunities for their use in cancer therapy.

Keywords: Bcl-2; apoptosis; c-Jun N-terminal kinase; colchicine; microtubule destabilising agents; vinca alkaloids.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimitotic Agents / adverse effects
  • Antimitotic Agents / pharmacology
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Humans
  • Microtubules / drug effects
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Tubulin Modulators / adverse effects
  • Tubulin Modulators / pharmacology*
  • Vinca Alkaloids / adverse effects
  • Vinca Alkaloids / pharmacology

Substances

  • Antimitotic Agents
  • Antineoplastic Agents
  • Tubulin Modulators
  • Vinca Alkaloids