Asciolla James J, Wu Xuewei, Adamopoulos Christos, Gavathiotis Evripidis, Poulikakos Poulikos I
Department of Oncological Sciences, Precision Immunology Institute, the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
China Innovation Center of Roche, Shanghai, China.
Nat Cancer. 2025 Jan;6(1):24-40. doi: 10.1038/s43018-024-00893-z. Epub 2025 Jan 30.
Cyclin-dependent kinases (CDKs) 4 and 6 (CDK4/6) are important regulators of the cell cycle. Selective CDK4/6 small-molecule inhibitors have shown clinical activity in hormonal receptor-positive (HR) metastatic breast cancer, but their effectiveness remains limited in other cancer types. CDK4/6 degradation and improved selectivity across CDK paralogs are approaches that could expand the effectiveness of CDK4/6 targeting. Recent studies also suggest the use of CDK4/6-targeting agents in cancer immunotherapy. In this Review, we highlight recent advancements in the mechanistic understanding and development of pharmacological approaches targeting CDK4/6. Collectively, these developments pose new challenges and opportunities for rationally designing more effective treatments.
细胞周期蛋白依赖性激酶4和6（CDK4/6）是细胞周期的重要调节因子。选择性CDK4/6小分子抑制剂已在激素受体阳性（HR）转移性乳腺癌中显示出临床活性，但它们在其他癌症类型中的有效性仍然有限。CDK4/6降解以及提高对CDK旁系同源物的选择性是可以扩大CDK4/6靶向治疗有效性的方法。最近的研究还表明，在癌症免疫治疗中可使用CDK4/6靶向药物。在本综述中，我们重点介绍了在针对CDK4/6的机制理解和药理学方法开发方面的最新进展。总的来说，这些进展为合理设计更有效的治疗方法带来了新的挑战和机遇。
