Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3'UTR mutation associated with increased expression in endometrial cancer. The results suggest multiple additional classes of cancer that may benefit from CDK4/6-inhibiting drugs such as abemaciclib.

中文翻译：

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激活D型细胞周期蛋白的基因组畸变与对CDK4和CDK6抑制剂Abemaciclib的敏感性增强相关。

大多数癌症保留了功能性视网膜母细胞瘤（Rb），因此可能对D细胞周期蛋白依赖性Rb激酶CDK4和CDK6的抑制产生反应。迄今为止，CDK4 / 6抑制剂已在乳腺癌和淋巴瘤中显示出令人鼓舞的临床活性，但尚不清楚哪些其他Rb阳性癌症可能会从这些药物中受益。没有系统的调查来比较肿瘤类型之间的相对敏感性和定义反应的分子决定因素的系统性描述。我们报告了对CDK4 / 6抑制高度敏感的癌症子集，其特征是已知各种基因组畸变可提高D-cyclin的水平，并描述了与子宫内膜癌表达增加相关的复发性CCND1 3'UTR突变。结果表明，其他多种类型的癌症可能会受益于抑制CDK4 / 6的药物（例如abemaciclib）。