Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center , 303 East Superior Street, Lurie 3-107, Chicago, IL 60611 , USA +1 312 5034267 ; +1 312 9081372 ;
Expert Opin Ther Targets. 2012 May;16(5):481-9. doi: 10.1517/14728222.2012.677439. Epub 2012 Apr 12.
The mammalian target of rapamycin (mTOR) signaling cascade is a key regulatory pathway controlling initiation of mRNA translation in mammalian cells. The mTOR inhibitor rapamycin and its derivatives have shown potent antineoplastic activities in many preclinical models and clinical trials. First-generation mTOR inhibitors are now FDA-approved for the treatment of renal cell carcinoma.
This article reviews the components of the mTOR pathway and their normal functions, highlighting the most common alterations in the pathway, seen in various human malignancies. It also discusses elements and effectors of this signaling cascade and reviews the therapeutic relevance of pharmacological inhibitors of the pathway in several malignancies, including lymphomas, leukemias, sarcomas, renal cell carcinoma, and breast cancer.
mTOR targeting is a highly promising therapeutic approach. First-generation mTOR inhibitors have already shown substantial activity in the treatment of certain tumors, while the emergence of second-generation catalytic mTOR inhibitors provides a better approach to target the pathway in malignant cells and has raised the potential for better clinical outcomes in the future.
哺乳动物雷帕霉素靶蛋白（mTOR）信号通路是控制哺乳动物细胞中 mRNA 翻译起始的关键调节途径。雷帕霉素及其衍生物等 mTOR 抑制剂在许多临床前模型和临床试验中表现出很强的抗肿瘤活性。第一代 mTOR 抑制剂现已获得 FDA 批准，用于治疗肾细胞癌。
本文综述了 mTOR 通路的组成部分及其正常功能，重点介绍了各种人类恶性肿瘤中该通路最常见的改变。本文还讨论了该信号级联的组成部分和效应子，并综述了该通路的药理学抑制剂在包括淋巴瘤、白血病、肉瘤、肾细胞癌和乳腺癌在内的几种恶性肿瘤中的治疗相关性。
mTOR 靶向治疗是一种很有前途的治疗方法。第一代 mTOR 抑制剂已在某些肿瘤的治疗中显示出显著的疗效，而第二代催化 mTOR 抑制剂的出现为靶向恶性细胞中的该通路提供了更好的方法，并有可能在未来获得更好的临床效果。
