RB-E2F信号通路与乳腺癌及其治疗

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RB E2F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。

The Roles of RB-E2F Pathways in Breast Cancer and Its Therapy

Mutations of retinoblastoma gene (RB1) and the related components regulating the CDK-RB-E2F pathway have been identified in almost all the human malignancies. Thus, normalizing cell cycle by cyclin-dependent kinase (CDK) inhibition has been emerging as a advanced method in cancer therapy. Until recently, the combination of CDK4/6 inhibitor palbociclib with aromatase inhibitors for the treatment of estrogen receptor-positive breast cancer is a successful clinical application. Many studies have illuminated that CDK-RB-E2F pathway has an essential role in controlling proliferation of breast cancer cell. Recent results have shown the additional functions of this pathway in tumor progression, angiogenesis and metastasis. Moreover, some E2Fs are the prognostic markers of breast cancer independent of the other clinical parameters. This review summarized the progression of RB-E2F pathway in breast cancer, and discussed the important interactions of CDK4/CDK6 inhibitors screened by the high throughput genomic study, aiming at developing more effective combination therapies.