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...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.展开更多
基金supported by the National Key R&D Program of China(No.2023YFC2706303)the National Natural Science Foundation of China(Nos.82373738 and 82304293)Natural Science Foundation of Jiangsu Province(Nos.SBK2024090146 and BK20221040).
文摘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.
