Miglarese Mark R, Carlson Robert O
Array BioPharma, Inc., 3200 Walnut Street, Boulder, CO 80301, USA.
Expert Opin Investig Drugs. 2006 Nov;15(11):1411-25. doi: 10.1517/13543784.15.11.1411.
Targeting cellular proliferation persists as a mainstay of cancer therapeutic strategy. Although microtubule-targeting drugs (such as taxanes and vinca alkaloids) have been used successfully in the clinic to treat a variety of cancers, they carry substantial liabilities that have spurred drug companies to aggressively pursue new tubulin-targeting drug candidates with improved efficacy and toxicity profiles. The recent discoveries of new mitotic targets for cancer therapy (such as kinesin spindle protein, Aurora kinases and Polo-like kinase-1) have also stimulated intense work focused on identifying novel antimitotic drugs directed at these new targets. A number of novel antimitotic drugs have demonstrated encouraging activity in preclinical models and have progressed into clinical development. This review focuses on selected new antimitotic drugs under evaluation in clinical trials.
靶向细胞增殖仍然是癌症治疗策略的核心。尽管微管靶向药物(如紫杉烷类和长春花生物碱)已在临床上成功用于治疗多种癌症,但它们存在诸多弊端,这促使制药公司积极研发具有更好疗效和毒性特征的新型微管蛋白靶向候选药物。癌症治疗新有丝分裂靶点(如驱动蛋白纺锤体蛋白、极光激酶和波罗样激酶-1)的近期发现,也激发了大量致力于鉴定针对这些新靶点的新型抗有丝分裂药物的研究工作。一些新型抗有丝分裂药物在临床前模型中已显示出令人鼓舞的活性,并已进入临床开发阶段。本综述聚焦于正在临床试验中评估的部分新型抗有丝分裂药物。