CNRS, UMR 6290, Équipe labellisée Ligue contre le Cancer 2014-2016, 35000 Rennes, France; Université de Rennes 1, Institut de Génétique et Développement de Rennes, 35000 Rennes, France.
CNRS, UMR 6290, Équipe labellisée Ligue contre le Cancer 2014-2016, 35000 Rennes, France; Université de Rennes 1, Institut de Génétique et Développement de Rennes, 35000 Rennes, France.
Trends Pharmacol Sci. 2017 Aug;38(8):687-700. doi: 10.1016/j.tips.2017.05.003. Epub 2017 Jun 7.
Aurora kinases control multiple events during cell cycle progression and are essential for mitotic and meiotic bipolar spindle assembly and function. There are three Aurora kinases in mammals, some of which have oncogenic properties and all of which are overexpressed in multiple cancers. Pharmaceutical companies quickly made these kinases priority targets for the development of inhibitors to be used as cancer treatments. In this review, we focus on Aurora A, against which several inhibiting compounds have been discovered and made available; however, even though some of these compounds underwent clinical trials, none have yet gone beyond Phase III trials. The varying efficiencies and particularities of these drugs raise several questions that are explored in this review: is Aurora A even a good target? What biomarkers can we use to measure its activity in vivo? How can we improve the Aurora A-inhibiting drugs?
极光激酶在细胞周期进程中控制多种事件，对于有丝分裂和减数分裂的双极纺锤体组装和功能至关重要。哺乳动物中有三种极光激酶，其中一些具有致癌特性，所有这些激酶在多种癌症中都过度表达。制药公司迅速将这些激酶作为开发抑制剂的优先目标，用于癌症治疗。在这篇综述中，我们重点介绍了 Aurora A，已经发现并提供了几种针对该激酶的抑制化合物；然而，尽管其中一些化合物已经进行了临床试验，但没有一种化合物已经超过 III 期临床试验。这些药物的效率和特点各不相同，提出了一些在本综述中探讨的问题：Aurora A 是否是一个好的靶点？我们可以使用哪些生物标志物来测量其在体内的活性？我们如何改进 Aurora A 抑制剂？
