CDK4/6 inhibitors are being used to treat a variety of human malignancies. In well-differentiated and dedifferentiated liposarcoma their clinical promise is associated with their ability to downregulate the MDM2 protein. The downregulation of MDM2 following treatment with CDK4/6 inhibitors also induces many cultured tumor cell lines derived from different types of malignancies to progress from quiescence into senescence. Here we used cultured human cell lines and defined a role for PDLIM7 and CDH18, regulating MDM2 protein in CDK4/6 inhibitor-treated cells. Materials from our previous phase II trials with palbociclib were then used to demonstrate that expression of CDH18 protein was associated with response, measured as both progression-free survival and overall survival. This supports the hypothesis that the biologic transition from quiescence to senescence has clinical relevance for this class of drugs.

中文翻译：

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在CDK4 / 6抑制剂治疗引起的衰老过程中，PDLIM7和CDH18调节MDM2的转换。

CDK4 / 6抑制剂被用于治疗多种人类恶性肿瘤。在高度分化和去分化的脂肪肉瘤中，它们的临床前景与它们下调MDM2蛋白的能力有关。用CDK4 / 6抑制剂处理后MDM2的下调也诱导了许多源自不同类型恶性肿瘤的培养肿瘤细胞系从静止发展到衰老。在这里，我们使用培养的人类细胞系，定义了PDLIM7和CDH18的作用，调节CDK4 / 6抑制剂处理的细胞中的MDM2蛋白。然后，使用我们先前使用palbociclib进行的II期临床试验的材料来证明CDH18蛋白的表达与反应相关，以无进展生存期和总体生存期来衡量。