A new perspective on old drugs: non-mitotic actions of tubulin-binding drugs play a major role in cancer treatment.
Microtubule-targeting agents (MTAs) are the most frequently used anti-cancer drugs. They can be divided into tubulin stabilizing and destabilizing agents. Their mode of action has been ascribed to their ability to interfere with the spindle apparatus and, thus, to block mitosis leading to tumor cell death. However, this view has been challenged in the last years and it became increasingly evident that non-mitotic actions of MTAs, i.e. their ability to affect the dynamics of interphase microtubules, are the most relevant mechanism underlying their efficacy. In this review we are presenting a distinct selection of examples of studies describing biological effects of MTAs in three areas: (i) mitosis-independent cell death and metastasis, (ii) tumor angiogenesis, and (iii) vascular-disrupting activity.
Institute of Pharmaceutical Biology, Biocenter, Goethe-University, Frankfurt am Main, Germany. fuerst@em.uni-frankfurt.de
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D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D012039:Regional Blood Flow / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators