© The Author 2006. Published by Oxford University Press.
EDITORIAL |
Can Mutations in 
-Actin Modulate the Toxicity of Microtubule Targeting Agents?
Affiliation of author: Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Correspondence to: Tito Fojo, MD, PhD, Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226, 9000 Rockville Pike, Bethesda, MD 20892 (e-mail: tfojo@helix.nih.gov).
| The first 150 words of the full text of this article appear below. |
So, how do microtubule targeting agents work, anyway? It is widely taught that stabilizing agents, such as paclitaxel, bind and stabilize microtubules, whereas destabilizing agents, such as vincristine, bind 
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-tubulin heterodimers or the ends of microtubules and prevent microtubule polymerization (1). However, Jordan and Wilson have long argued that, when used at the low concentrations that kill cells, both stabilizing and destabilizing agents suppress microtubule dynamics, and that it is this change in microtubule dynamics that is important (1,2). Under either scenario, mitotic arrest ensues and is then followed by cell death. In this issue of the Journal, Verrills et al. (3) argue that 
-actin is essential for the efficacy of microtubule targeting agents and that, by affecting the activity of microtubule targeting agents, alterations in -actin constitute a novel mechanism of resistance to microtubule targeting agents. Can this