Targeting CDK4 and CDK6 in cancer.
Targeting CDK4 and CDK6 in cancer.
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DOI：
10.1038/s41568-022-00456-3
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发表时间：
2022-06
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影响因子：
--
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细胞周期蛋白依赖性激酶（CDK）4和CDK 6（CDK 4/6）是细胞过渡到S期的关键介质，对许多癌症类型的发生、生长和存活都很重要。CDK 4/6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护理标准。正如预期的那样，CDK 4/6抑制剂将敏感的肿瘤细胞阻滞在细胞周期的G1期。然而，CDK 4/6抑制的影响要广泛得多。对其作用机制的新见解引发了对新治疗机会的识别，包括开发新的联合方案，将应用扩展到更广泛的癌症，并用作支持性护理以改善其他疗法的毒性。在诊所中探索这些新的机会是一个紧迫的优先事项，在许多情况下，这一问题尚未得到充分解决。在这里，我们提供了一个概念化CDK 4/6抑制剂在癌症中的活性的框架，并解释了这个框架如何塑造这些药物的未来临床开发。我们还讨论了CDK 4/6抑制剂耐药性的生物学基础，这是临床肿瘤学中越来越常见的挑战。
Cyclin-dependent kinase (CDK) 4 and CDK6 (CDK4/6) 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 toxicity 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 conceptualising 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 biologic underpinnings of CDK4/6 inhibitor resistance, an increasingly common challenge in clinical oncology.
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影响因子：
50.3
作者：
Barbash, Olena;Zamfirova, Petia;Lin, Douglas I.;Chen, Xiangmei;Yang, Ke;Nakagawa, Hiroshi;Lu, Fengmin;Rustgi, Anil K.;Diehl, J. Alan
通讯作者：
Diehl, J. Alan
影响因子：
50.3
作者：
Anders L;Ke N;Hydbring P;Choi YJ;Widlund HR;Chick JM;Zhai H;Vidal M;Gygi SP;Braun P;Sicinski P
通讯作者：
Sicinski P
影响因子：
8.6
作者：
Brand, Matthias;Jiang, Baishan;Winter, Georg E.
通讯作者：
Winter, Georg E.
影响因子：
5.7
作者：
Bisi, John E.;Sorrentino, Jessica A.;Strum, Jay C.
通讯作者：
Strum, Jay C.
影响因子：
3.7
作者：
Barton KL;Misuraca K;Cordero F;Dobrikova E;Min HD;Gromeier M;Kirsch DG;Becher OJ
通讯作者：
Becher OJ