作者:罗婷 副教授,医学博士/博士后 硕士生导师;四川大学华西医院乳腺 疾病临床研究中心/肿瘤科 。 1. 背景 CDKs主要分为两类:一类参与细胞周期调控,主要包括CDK1、CDK2、CDK4、CDK6等;另一大类参与转录调节,主要包括CDK7、CDK8、CDK9、CDK10、CDK11等。 图2. CyclinD-CDK4/6-Rb调控轴信号通路异常导致CDK4/6抑制剂耐药[13] 2.上市及在研CDK4/6抑制剂 国内CDK4/6抑制剂开发速度最快的为江苏恒瑞开发的SHR6390,目前已经进入临床III期。进入II期临床的有3个,分别是贝达药业的BPI-1178、重庆复创的FCN-437、兆科肿瘤药物的Zotiraciclib。进入到临床I期的品种超过10个,如上海君实生物、基石药业、贝达药业、正大天晴、江苏豪森、四环医药、复星医药等公司均有品种布局。 [1]Siegel RL, Miller KD and Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin. 2020;70(1):7-30. [2]Dai X, Li T, Bai Z, et al. Breast cancer intrinsic subtype classification, clinical use and future trends[J]. Am J Cancer Res. 2015;5(10):2929-43. [3]Cardoso F, Costa A, Senkus E, et al. 3rd ESO-ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)[J]. Breast. 2017;31:244-59. [4]Clarke R, Tyson JJ and Dixon JM. Endocrine resistance in breast cancer--An overview and update[J]. Mol Cell Endocrinol. 2015;418 Pt 3:220-34. [5]Brufsky AM and Dickler MN. 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