The Louis V. Gerstner Graduate School of Biomedical Sciences and the Sloan Kettering Institute Program in Molecular Biology, Memorial Sloan Kettering Cancer Center, RRL917C, Box 207, 1275 York Avenue, New York, NY 10065, USA.
Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Cancer Cell. 2018 Jul 9;34(1):9-20. doi: 10.1016/j.ccell.2018.03.023. Epub 2018 May 3.
CDK4/6 inhibitors are among a new generation of therapeutics. Building upon the striking success of the combination of CDK4/6 inhibitors and the hormone receptor antagonist letrozole in breast cancer, many other combinations have recently entered clinical trials in multiple diseases. To achieve maximal benefit with CDK4/6 inhibitors it will be critical to understand the cellular mechanisms by which they act. Here we highlight the mechanisms by which CDK4/6 inhibitors can exert their anti-tumor activities beyond simply enforcing cytostatic growth arrest, and discuss how this knowledge may inform new combinations, improve outcomes, and modify dosing schedules in the future.
CDK4/6 抑制剂属于新一代治疗药物。基于 CDK4/6 抑制剂与激素受体拮抗剂来曲唑联合应用在乳腺癌中的显著成功，许多其他联合方案最近已在多种疾病中进入临床试验。为了从 CDK4/6 抑制剂中获得最大获益，理解其作用的细胞机制至关重要。在这里，我们重点介绍 CDK4/6 抑制剂除了单纯执行细胞周期停滞之外发挥抗肿瘤活性的机制，并讨论这些知识如何为新的联合方案提供信息，改善结果，并在未来修改给药方案。
