CDK4/6抑制剂在非小细胞肺癌治疗中的研究进展

Research Progress of CDK4/6 Inhibitors in Non-small Cell Lung Cancer

肺癌是全球癌症相关死亡的首要原因,非小细胞肺癌(non-small cell lung cancer, NSCLC)占肺癌的80%-85%。恶性肿瘤可以无限增殖,细胞周期失调控是恶性肿瘤特征之一。细胞周期依赖激酶(cyclin D-dependent kinase,CDK)4/6抑制剂能阻滞肿瘤细胞通过G1期进入S期从而抑制肿瘤增殖,该药物在激素受体阳性乳腺癌中取得了良好的疗效,联合内分泌治疗成为这类患者一线标准治疗。细胞周期失控在NSCLC中比较常见,发生率约为22%-45%,CDK4/6抑制剂也进行了一系列的探索研究,并取得一定的效果,将来有可能成为新的治疗手段。本文重点讨论CDK4/6抑制剂在NSCLC的研究进展,包括作用机制、获批药物、在NSCLC中的临床研究进展、疗效预测生物标记物及局限性等。

Lung cancer is the leading cause of cancer-related death worldwide.Non-small cell lung cancer(NSCLC)accounts for 80%-85%of lung cancer.Malignant tumors can proliferate indefinitely,and cell cycle regulation is abnormal which is one of the characteristics of malignant tumor.Cyclin D-dependent kinase(CDK)4/6 inhibitor can prevent tumor cells from entering S phase through G1 phase and inhibit tumor proliferation.The CDK4/6 inhibitor has achieved good effect in hormone receptor positive breast cancer,and CDK4/6 inhibitor combined with endocrine therapy has become a standard treatment for this kind of patients.Cell cycle regulation is usually abnormal in NSCLC,which incidence is about 22%-45%.CDK4/6 inhibitors have also carried out a series of research and achieved some results,which may become a new treatment in the future.This review focuses on the research progress of CDK4/6 inhibitors in NSCLC,including the mechanism and the approved drugs,clinical research progress in NSCLC,biomarkers for efficacy prediction and current limitations.