Liu Jia, Li Hui-Qing, Zhou Fu-Xia, Yu Jie-Wen, Sun Ling, Han Zhong-Hou
Maternal and Child Health Hospital of Qinhuangdao, Qinhuangdao, P.R. China.
Tumour Biol. 2017 Jun;39(6):1010428317710825. doi: 10.1177/1010428317710825.
Mechanistic target of rapamycin controls cell growth, metabolism, and aging in response to nutrients, cellular energy stage, and growth factors. In cancers including breast cancer, mechanistic target of rapamycin is frequently upregulated. Blocking mechanistic target of rapamycin with rapamycin, first-generation and second-generation mechanistic target of rapamycin inhibitors, called rapalogs, have shown potent reduction of breast cancer tumor growth in preclinical models and clinical trials. In this review, we summarize the fundamental role of the mechanistic target of rapamycin pathway in driving breast tumors. Moreover, we also review key molecules involved with aberrant mechanistic target of rapamycin pathway activation in breast cancer and current efforts to target these components for therapeutic gain. Further development of predictive biomarkers will be useful in the selection of patients who will benefit from inhibition of the mechanistic target of rapamycin pathway.
雷帕霉素作用机制靶点可根据营养物质、细胞能量状态和生长因子来控制细胞生长、代谢及衰老。在包括乳腺癌在内的多种癌症中，雷帕霉素作用机制靶点常常上调。使用雷帕霉素、第一代和第二代雷帕霉素作用机制靶点抑制剂（即雷帕霉素类似物）阻断雷帕霉素作用机制靶点，已在临床前模型和临床试验中显示出能有效抑制乳腺癌肿瘤生长。在本综述中，我们总结了雷帕霉素作用机制靶点通路在驱动乳腺肿瘤方面的基本作用。此外，我们还综述了与乳腺癌中雷帕霉素作用机制靶点通路异常激活相关的关键分子，以及目前针对这些成分以获得治疗益处所做的努力。进一步开发预测性生物标志物将有助于选择能从抑制雷帕霉素作用机制靶点通路中获益的患者。
