Microtubule destabilising agents: far more than just antimitotic anticancer drugs.
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.
Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
Darcy
D
Bates
Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
Alan
A
Eastman
D000818:Animals; D050256:Antimitotic Agents / Q000009:adverse effects / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D050257:Tubulin Modulators / Q000009:adverse effects / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000009:adverse effects / Q000494:pharmacology
D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D014748:Vinca Alkaloids
Bcl-2; apoptosis; c-Jun N-terminal kinase; colchicine; microtubule destabilising agents; vinca alkaloids