CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest.

CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest.
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DOI:
10.1016/j.tcb.2018.07.002
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发表时间:
2018-11
影响因子:
19
通讯作者:
Zhao JJ
Zhao JJ
中科院分区:
生物学1区
文献类型:
--
作者:
Goel S;DeCristo MJ;McAllister SS;Zhao JJ

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细胞周期蛋白依赖性激酶4和6的药物抑制物(CDK4/6)最近进入临床肿瘤学家的治疗领域,在乳腺癌和其他癌症患者中显示出良好的活性。虽然它们的主要作用机制是抑制视网膜母细胞瘤(RB)蛋白的磷酸化,从而诱导细胞周期停滞,但CDK4/6抑制剂以其他方式改变癌细胞生物学,也可以用于治疗。这些包括丝裂原激酶信号的调节,衰老样表型的诱导,以及癌细胞免疫原性的增强。在这里,我们描述了CDK4/6抑制剂对癌细胞的较少认识的作用,并提出了利用它们来增强这些药物对癌症患者的益处的方法。
Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have recently entered the therapeutic armamentarium of clinical oncologists, and show promising activity in patients with breast and other cancers. Although their chief mechanism of action is inhibition of Retinoblastoma (RB) protein phosphorylation and thus induction of cell cycle arrest, CDK4/6 inhibitors alter cancer cell biology in other ways that can also be leveraged for therapeutic benefit. These include modulation of mitogenic kinase signaling, induction of a senescence-like phenotype, and enhancement of cancer cell immunogenicity. Here, we describe the lesser appreciated effects of CDK4/6 inhibitors on cancer cells, and suggest ways by which they might be exploited to enhance the benefits of these agents for cancer patients.
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