Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
Int J Cancer. 2020 Dec 1;147(11):2988-2995. doi: 10.1002/ijc.33054. Epub 2020 May 30.
The regulation and function of cyclin-dependent kinase 6 (CDK6)- and cyclin-dependent kinase 4 (CDK4)-cyclin complexes are commonly altered with enhanced kinase activity found in hematopoietic malignancies, breast cancer and melanoma making CDK4 and CDK6 attractive targets for therapeutic interference. Although dual CDK4/6 inhibitors have revolutionized treatment of breast cancer patients and reveal promising results in several solid tumors and hematological malignancies, there is a need for novel compounds targeting the versatile kinase-independent functions of CDK6 to improve cancer treatment. The following review summarizes the latest findings on CDK6 in cancer development and discusses novel therapeutic approaches to selectively inhibit CDK6s function as a transcriptional regulator.
细胞周期蛋白依赖性激酶 6（CDK6）-和细胞周期蛋白依赖性激酶 4（CDK4）-细胞周期蛋白复合物的调节和功能通常会发生改变，在血液恶性肿瘤、乳腺癌和黑色素瘤中发现激酶活性增强，这使得 CDK4 和 CDK6 成为治疗干预的有吸引力的靶点。尽管双重 CDK4/6 抑制剂已经彻底改变了乳腺癌患者的治疗方法，并在几种实体瘤和血液恶性肿瘤中显示出有希望的结果，但仍需要针对 CDK6 多功能激酶非依赖性功能的新型化合物来改善癌症治疗。本文综述了 CDK6 在癌症发展中的最新研究结果，并讨论了选择性抑制 CDK6 作为转录调节剂功能的新型治疗方法。
