摘要The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for can-cer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no se-lectivity 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 develop-ment 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 in-hibitors and selective CDK2 inhibitors,which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.