Overcoming resistance to CDK4/6 inhibitors is a major clinical challenge. In this issue of Cancer Cell, Freeman-Cook et al. study mechanisms of resistance to CDK4/6 inhibitors by employing a CRISPRa screen. They identify the cyclin E-CDK2 axis and Myc signaling as key pathways of resistance and develop PF-06873600, a selective CDK2/4/6 inhibitor.

中文翻译：

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在细胞周期边界恢复秩序：共同靶向 CDK4/6 和 CDK2

克服对 CDK4/6 抑制剂的耐药性是一项重大的临床挑战。在本期《癌细胞》中，Freeman-Cook 等人。通过采用 CRISPRa 筛选研究对 CDK4/6 抑制剂的抗性机制。他们将 cyclin E-CDK2 轴和 Myc 信号转导确定为耐药的关键途径，并开发了 PF-06873600，一种选择性 CDK2/4/6 抑制剂。