CDK4/6抑制剂耐药机制的研究进展

细胞周期依赖性激酶4/6（cyclin-dependent kinase 4/6,CDK4/6)抑制剂能作用于过度活化的CDK4/6，恢复正常细胞周期，并通过触发免疫，改变肿瘤微环境等发挥抗肿瘤作用。目前，CDK4/6抑制剂的问世极大地改善了激素受体阳性（hormone receptor-positive,HR+）、人表皮生长因子受体2阴性（human epidermal growth factor receptor 2-negative,HER2-)晚期乳腺癌患者的预后，使无进展生存期(progression-free-survival,PFS)增加近一倍，且不良反应可控。尽管如此，这类患者最终仍会因CDK4/6抑制剂耐药而出现疾病进展。CDK4/6抑制剂的耐药机制十分复杂，尚未完全明确。预测其早期耐药或治疗敏感的生物标记物也有待确定。本文对CDK4/6抑制剂治疗的作用机制及耐药机制进行梳理和总结，并对疾病进展后的治疗策略作简要讨论。

Research progresson on resistance mechanism of CDK4/6 inhibitors

Cyclin-dependent kinase 4/6(CDK4/6) inhibitors act on CDK4/6 that is over activated.CDK4/6 inhibitors play anti-tumor roles by restoring normal cell cycle,enhancing anti-tumor immunity,and reforming tumor microenvironment.Currently,the advent of CDK4/6 inhibitors has greatly improved the prognosis of patients with hormone receptor-positive(HR+),human epidermal growth factor receptor 2-negative(HER2-) advanced breast cancer,nearly doubling progression-free survival(PFS) and controllable adverse reactions.However,these patients eventually develop disease progression due to CDK4/6 inhibitor resistance.The mechanisms of resistance to CDK4/6 inhibitors are complex and not fully defined.Biomarkers that predict early resistance or treatment sensitivity also need to be determined.The mechanism of action and mechanisms of drug-resistance of CDK4/6 inhibitors were reviewed and summarized in this paper,and the treatment strategies after the disease progression were briefly discussed.