细胞周期依赖性激酶4/6抑制剂在恶性肿瘤治疗中的应用及耐药机制  

Application of Cyclin-dependent Kinase 4/6 Inhibitors in the Treatment of Malignancies and the Mechanism of Drug Resistance

作　　者：唐辉 应红艳[1] 白春梅[1] TANG Hui;YING Hong-yan;BAI Chun-mei(Department of Medical Oncology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院肿瘤内科,北京100730

出　　处：《协和医学杂志》2020年第6期758-765,共8页Medical Journal of Peking Union Medical College Hospital

基　　金：中国医学科学院医学与健康科技创新工程(2016-12M-1-001)。

摘　　要：增殖失控是恶性肿瘤的重要特征之一。细胞周期依赖性激酶4/6(cyclin-dependentkinase 4/6,CDK4/6)抑制剂能作用于各种原因导致的过度活化的CDK4/6,恢复正常细胞周期,并可通过增强免疫、改变肿瘤微环境等发挥抗肿瘤作用。目前,CDK4/6抑制剂在激素受体阳性乳腺癌治疗中取得了良好疗效,已被批准联合内分泌治疗作为此类肿瘤的一线治疗方案,在其他肿瘤中的应用亦逐渐开展,疗效有待验证。对CDK4/6抑制剂天然或获得性耐药是影响其疗效的重要因素,目前激素受体阳性(主要为雌激素受体阳性)能较为准确预测内分泌联合CDK4/6抑制剂治疗的反应性,其他标志物需进一步探索和验证。本文对CDK4/6抑制剂治疗恶性肿瘤的作用机制、应用现状及耐药机制进行梳理和总结,并对当前CDK4/6抑制剂治疗乳腺癌尚存争议的临床决策问题作简要讨论。Uncontrolled cell proliferation is one of the important hallmarks of malignancies.Cyclin-dependent kinase 4/6(CDK4/6)inhibitors act on CDK4/6 that is over activated by various causes.CDK4/6 inhibitors play anti-tumor roles by restoring normal cell cycle,enhancing anti-tumor immunity,and reforming tumor microenvironment.Currently,CDK4/6 inhibitors have been confirmed to be effective in hormonereceptor-positive breast cancer and were approved as the first-line treatment for this breast cancer in combination with endocrine therapy.Furthermore,CDK4/6 inhibitors have been gradually applied to the treatment of other tumors,but the efficacy remains to be evaluated.Natural or acquired resistance to CDK4/6 inhibitors is a major factor affecting their efficacy.However,at present,only hormone receptor-positive(mainly estrogen receptorpositive)can relatively accurately predict the responsiveness of CDK4/6 inhibitors in combination with endocrine treatment,and other markers need to be further explored and verified in clinical studies.The mechanism of action,the status of application,and mechanisms of drug-resistance of CDK4/6 inhibitors in the treatment of malignancies were reviewed and summarized in this paper,and the controversy over clinical decision-making on the treatment of breast cancer with CDK4/6 inhibitors was briefly discussed.

关 键 词：细胞周期依赖性激酶4/6抑制剂 细胞周期调控 乳腺癌 治疗 耐药机制 

分 类 号：R73[医药卫生—肿瘤]