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

Microtubule destabilising agents: far more than just antimitotic anticancer drugs

Darcy Bates  1 , Alan Eastman  2
Affiliations
Review

Microtubule destabilising agents: far more than just antimitotic anticancer drugs

Darcy Bates et al. Br J Clin Pharmacol. 2017 Feb.

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.

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Figures

Figure 1
Figure 1
Consequences of microtubule disruption
Figure 2
Figure 2
Mechanisms of acute apoptosis. Acute, cell cycle independent apoptosis in response to microtubule destabilising agents (MDAs) may be unique to hematopoietic cells. The target of JNK in this model is currently unknown but it is proposed that Bcl‐2 lies downstream of JNK. Bcl‐2 phosphorylation has not been seen in this model. (A) MDA + Bcl‐2 inhibitor = Noxa‐dependent; (B) MDA Alone = Noxa‐ and JNK‐dependent; (C) MDA + Mcl‐1 inhibitor = JNK‐dependent
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