文章：

靶向CDK4和CDK6在癌症中的作用

Targeting CDK4 and CDK6 in cancer

原文发布日期：2022-03-18

DOI: 10.1038/s41568-022-00456-3

类型: Review Article

开放获取: 否

英文摘要：

Cyclin-dependent kinase 4 (CDK4) and CDK6 are critical mediators of cellular transition into S phase and are important for the initiation, growth and survival of many cancer types. Pharmacological inhibitors of CDK4/6 have rapidly become a new standard of care for patients with advanced hormone receptor-positive breast cancer. As expected, CDK4/6 inhibitors arrest sensitive tumour cells in the G1 phase of the cell cycle. However, the effects of CDK4/6 inhibition are far more wide-reaching. New insights into their mechanisms of action have triggered identification of new therapeutic opportunities, including the development of novel combination regimens, expanded application to a broader range of cancers and use as supportive care to ameliorate the toxic effects of other therapies. Exploring these new opportunities in the clinic is an urgent priority, which in many cases has not been adequately addressed. Here, we provide a framework for conceptualizing the activity of CDK4/6 inhibitors in cancer and explain how this framework might shape the future clinical development of these agents. We also discuss the biological underpinnings of CDK4/6 inhibitor resistance, an increasingly common challenge in clinical oncology.

摘要翻译： 

细胞周期蛋白依赖性激酶4（CDK4）和CDK6是细胞进入S期的关键介导因子，对多种癌症的发生、生长和存活具有重要作用。CDK4/6的药理学抑制剂已迅速成为晚期激素受体阳性乳腺癌患者的新标准治疗方案。正如预期那样，CDK4/6抑制剂能将敏感肿瘤细胞阻滞在细胞周期的G1期。然而，CDK4/6抑制的作用远不止于此。对其作用机制的新认识催生了新的治疗机遇，包括开发新型联合治疗方案、拓展至更广泛癌症类型的应用，以及作为支持治疗以减轻其他疗法的毒副作用。在临床中探索这些新机遇是当务之急，而许多领域尚未得到充分研究。本文提出了构建CDK4/6抑制剂抗癌作用的概念框架，并阐释该框架如何指导此类药物的未来临床开发。同时，我们还探讨了CDK4/6抑制剂耐药性的生物学基础——这一临床肿瘤学中日益常见的挑战。

原文链接：

Targeting CDK4 and CDK6 in cancer