Antimitotic drugs in cancer chemotherapy: Promises and pitfalls

被引:74
作者
Marzo, Isabel [1 ]
Naval, Javier [1 ]
机构
[1] Univ Zaragoza, Fac Ciencias, Dept Bioquim & Biol Mol & Celular, Zaragoza 50009, Spain
关键词
Mitosis; Cancer; Chemotherapy; DEPENDENT KINASE INHIBITOR; SPINDLE PROTEIN INHIBITOR; SMALL-MOLECULE INHIBITOR; RESISTANT PROSTATE-CANCER; PHASE-I; ANTITUMOR-ACTIVITY; AURORA KINASE; DOSE-ESCALATION; MITOTIC ARREST; CDK INHIBITOR;
D O I
10.1016/j.bcp.2013.07.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cancer cells usually display higher proliferation rates than normal cells. Some currently used antitumor drugs, such as vinca alkaloids and taxanes, act by targeting microtubules and inhibiting mitosis. In the last years, different mitotic regulators have been proposed as drug target candidates for antitumor therapies. In particular, inhibitors of Cdks, Chks, Aurora kinase and Polo-like kinase have been synthesized and evaluated in vitro and in animal models and some of them have reached clinical trials. However, to date, none of these inhibitors has been still approved for use in chemotherapy regimes. We will discuss here the most recent preclinical information on those new antimitotic drugs, as well as the possible molecular bases underlying their lack of clinical efficiency. Also, advances in the identification of other mitosis-related targets will be also summarized. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:703 / 710
页数:8
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