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视网膜母细胞瘤基因(retinoblastoma gene,RB1)突变或调节CDK-RB-E2F通路其他成分的突变存在于几乎所有人类恶性肿瘤中。因此,通过抑制细胞周期蛋白激酶(CDK)来实现对细胞周期的调控,在肿瘤治疗中越来越显示出其优势。目前,CDK4/6抑制剂帕博西尼(palbociclib)联合芳香酶抑制剂,治疗ER-阳性乳腺癌是很有效的临床应用。研究显示,CDK-RB-E2F信号通路,对控制乳腺细胞增殖发挥关键作用。近期的研究结果,揭示了该通路在肿瘤发展、血管生成及转移中的作用。并且,E2Fs是不依赖于其他临床参数的乳腺癌预后指标。本综述总结了乳腺癌中RBE2F通路的最新研究进展,并且讨论应用高通量基因组学研究,筛选获得乳腺癌中CDK4/6抑制剂重要的作用靶点,旨在发展更有效的联合治疗手段。
Mutations in retinoblastoma gene (RB1) mutations or other components that regulate the CDK-RB-E2F pathway are present in almost all human malignancies. Therefore, the regulation of the cell cycle by inhibiting cyclin kinases (CDKs) has increasingly shown its advantages in tumor therapy. Currently, CDK4 / 6 inhibitor palbociclib combined with aromatase inhibitors, the treatment of ER-positive breast cancer is a very effective clinical application. Studies have shown that the CDK-RB-E2F signaling pathway plays a key role in controlling breast cell proliferation. Recent findings reveal the role of this pathway in tumor development, angiogenesis and metastasis. Moreover, E2Fs are prognostic indicators of breast cancer independent of other clinical parameters. This review summarizes recent advances in the RBE2F pathway in breast cancer and discusses the use of high-throughput genomics studies to screen for important targets of CDK4 / 6 inhibitors in breast cancer to develop more effective combination therapies.