Qi Jiating, Ouyang Zhuqing
The Second Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Biomedicines. 2022 Mar 16;10(3):685. doi: 10.3390/biomedicines10030685.
Cyclin-dependent kinase 4/6 (CDK4/6) are key regulators of the cell cycle and are deemed as critical therapeutic targets of multiple cancers. Various approaches have been applied to silence CDK4/6 at different levels, i.e., CRISPR to knock out at the DNA level, siRNA to inhibit translation, and drugs that target the protein of interest. Here we summarize the current status in this field, highlighting the mechanisms of small molecular inhibitors treatment and drug resistance. We describe approaches to combat drug resistance, including combination therapy and PROTACs drugs that degrade the kinases. Finally, critical issues and perspectives in the field are outlined.
细胞周期蛋白依赖性激酶4/6（CDK4/6）是细胞周期的关键调节因子，被视为多种癌症的关键治疗靶点。人们已采用各种方法在不同水平使CDK4/6沉默，即在DNA水平通过CRISPR敲除、通过小干扰RNA（siRNA）抑制翻译以及使用靶向相关蛋白的药物。在此，我们总结该领域的现状，重点介绍小分子抑制剂治疗的机制和耐药性。我们描述了对抗耐药性的方法，包括联合治疗和可降解激酶的蛋白水解靶向嵌合体（PROTAC）药物。最后，概述了该领域的关键问题和前景。
