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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

唐辉 应红艳 白春梅

唐辉, 应红艳, 白春梅. 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[J]. 协和医学杂志, 2020, 11(6): 758-765. doi: 10.3969/j.issn.1674-9081.2020.06.022
引用本文: 唐辉, 应红艳, 白春梅. 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[J]. 协和医学杂志, 2020, 11(6): 758-765. doi: 10.3969/j.issn.1674-9081.2020.06.022
TANG Hui, YING Hong-yan, BAI Chun-mei. Application of Cyclin-dependent Kinase 4/6 Inhibitors in the Treatment of Malignancies and the Mechanism of Drug Resistance[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(6): 758-765. doi: 10.3969/j.issn.1674-9081.2020.06.022
Citation: TANG Hui, YING Hong-yan, BAI Chun-mei. Application of Cyclin-dependent Kinase 4/6 Inhibitors in the Treatment of Malignancies and the Mechanism of Drug Resistance[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(6): 758-765. doi: 10.3969/j.issn.1674-9081.2020.06.022

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

doi: 10.3969/j.issn.1674-9081.2020.06.022
基金项目: 

中国医学科学院医学与健康科技创新工程 2016-12M-1-001

详细信息
    通讯作者:

    应红艳  电话:010-69158764, E-mail:yinghy15@163.com

  • 中图分类号: R73

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

Funds: 

Medical and Health Science and Technology Innovation Engineering, Chinese Academy of Medical Sciences 2016-12M-1-001

More Information
    Corresponding author: YING Hong-yan  Tel: 86-10-69158764, E-mail:yinghy15@163.com
  • 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-dependent kinase 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。
    作者贡献:唐辉负责文献检索、数据分析、示意图绘制、论文撰写;应红艳参与文献检索、数据分析、论文修改;白春梅提供修改建议并帮助修改论文。
    利益冲突  无
  • 图  1  细胞周期依赖性激酶4/6调节细胞周期进程及其活性影响因素示意图

    PTEN:10号染色体上缺失的磷酸酶与张力蛋白同源物蛋白;FGFR1:纤维细胞生长因子受体1;MAPK:丝裂原活化蛋白激酶;PI3K:磷脂酰肌醇3-激酶;Akt:蛋白激酶B;mTOR:哺乳动物雷帕霉素靶蛋白;AP-1:激活蛋白-1;cyclin:细胞周期蛋白;CDK:细胞周期依赖性激酶;INK4:CDK4抑制因子;CIP/KIP:CDK相互作用蛋白/激酶抑制蛋白;MDM2:鼠双微基因2;RB1:视网膜母细胞瘤蛋白1;E2F:腺病毒2区早期结合因子;FAT1:脂肪非典型钙黏蛋白1

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  • 收稿日期:  2020-06-05
  • 录用日期:  2020-07-20
  • 刊出日期:  2020-11-30

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