通过抑制细胞周期蛋白依赖性激酶（CDKs）调控细胞周期用于癌症治疗的最新进展。

Recent advances in regulating the cell cycle through inhibiting CDKs for cancer treatment.

作者信息

Chen Weijiao, Zhuang Xujie, Chen Yuanyuan, Yang Huanaoyu, Shen Linhu, Feng Sikai, Min Wenjian, Yuan Kai, Yang Peng

机构信息

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

出版信息

Chin J Nat Med. 2025 Mar;23(3):286-298. doi: 10.1016/S1875-5364(25)60846-6.

DOI:10.1016/S1875-5364(25)60846-6

PMID:40122659

Abstract

The inhibition of cyclin-dependent kinases (CDKs) is considered a promising strategy for cancer treatment due to their role in cell cycle regulation. However, CDK inhibitors with no selectivity among CDK families have not been approved. A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market. Subsequently, resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment. In this review, we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors. Moreover, we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors, which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.

摘要

由于细胞周期蛋白依赖性激酶（CDKs）在细胞周期调控中的作用，抑制CDKs被认为是一种很有前景的癌症治疗策略。然而，对CDK家族无选择性的CDK抑制剂尚未获批。一种对CDK4/6具有高选择性的CDK抑制剂对乳腺癌显示出显著的治疗效果，并已成为市场上的重磅炸弹。随后，耐药性逐渐降低了选择性CDK4/6抑制剂在乳腺癌治疗中的疗效。在本综述中，我们首先介绍选择性CDK4/6抑制剂的发展，然后解释CDK2激活在诱导对CDK4/6抑制剂耐药中的作用。此外，我们重点关注CDK2/4/6抑制剂和选择性CDK2抑制剂的发展，这将有助于未来发现靶向细胞周期的新型CDK抑制剂。