Anticancer Therapeutic Strategies Based on CDK Inhibitors
Anticancer Therapeutic Strategies Based on CDK Inhibitors
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DOI：
10.2174/13816128113199990377
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发表时间：
2013-09-01
影响因子：
3.1
通讯作者：
Giordano, Antonio
中科院分区：
文献类型：
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作者：
Esposito, Luca;Indovina, Paola;Giordano, Antonio
正常的细胞周期进程由细胞周期蛋白依赖性激酶（CDK）的顺序作用控制，其活性取决于它们与调节伴侣（细胞周期蛋白）的结合。细胞周期失调是正常细胞转化为肿瘤细胞的第一步。事实上，大多数癌细胞在控制CDK活性的通路成员中携带突变。因此，该激酶家族是开发癌症治疗新药的关键靶标。最近，ATP竞争性CDK抑制剂和最新一代的非ATP竞争性抑制剂正在成为靶向治疗的有前途的药物。许多临床试验正在进行中，使用CDK抑制剂作为单一药物以及与传统细胞毒性药物组合。在这篇综述中，我们将讨论基于CDK抑制剂在癌症中的应用的新的治疗策略。
Normal cell cycle progression is controlled by the sequential action of cyclin-dependent kinases (CDKs), the activity of which depends on their binding to regulatory partners (cyclins). Deregulation of cell cycle is one of the first steps that transform normal cells into tumor cells. Indeed, most cancer cells bear mutations in members of the pathways that control the CDK activity. For this reason, this kinase family is a crucial target for the development of new drugs for cancer therapy. Recently, both ATP-competitive CDK inhibitors and the last generation of non-ATP-competitive inhibitors are emerging as promising agents for targeted therapies. Many clinical trials are in progress, using CDK inhibitors both as single agents and in combination with traditional cytotoxic agents. In this review, we will discuss new therapeutic strategies based on the use of CDK inhibitors in cancer.