Sablin Marie-Paule, Ricci Francesco, Loirat Delphine, Jobard Aude, Basse Clémence, Romano Emanuela, Le Tourneau Christophe, Dieras Véronique
Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France.
Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France.
Bull Cancer. 2017 Feb;104(2):114-122. doi: 10.1016/j.bulcan.2016.12.005. Epub 2017 Jan 23.
Dysregulation of cellular cycle is a key component of carcinogenesis and its targeting represents an interesting approach. Recently, the development of selective inhibitors of the cycle targeting the cyclin-dependent kinases (CDK) 4 and 6 revived interest in this therapeutic class after the failure of pan-inhibitors. Palbociclib, ribociclib, and abemaciclib are the 3 drugs with the most advanced development. They demonstrated preclinical activity in luminal breast cancer models and are under clinical evaluation. The first available studies demonstrate the value of these compounds with an improved prognosis of metastatic patients in combination with endocrine therapy (palbociclib, ribociclib) or in monotherapy (abemaciclib). The results of ongoing studies will clarify the role of these agents in our new strategies and the individualisation of biomarkers will help to define patients who benefit most from this approach.
细胞周期失调是致癌作用的关键组成部分,针对该靶点是一种有趣的治疗方法。最近,在泛抑制剂失败后,靶向细胞周期蛋白依赖性激酶(CDK)4和6的选择性抑制剂的开发重新引发了对这一治疗类别的兴趣。帕博西尼、瑞博西尼和阿贝西利是研发进展最为领先的3种药物。它们在管腔型乳腺癌模型中显示出临床前活性,目前正在进行临床评估。首批可得研究证明了这些化合物的价值,联合内分泌治疗(帕博西尼、瑞博西尼)或单药治疗(阿贝西利)可改善转移性患者的预后。正在进行的研究结果将阐明这些药物在我们新策略中的作用,生物标志物的个体化将有助于确定最能从这种方法中获益的患者。