Conciatori Fabiana, Ciuffreda Ludovica, Bazzichetto Chiara, Falcone Italia, Pilotto Sara, Bria Emilio, Cognetti Francesco, Milella Michele
Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome 00144, Italy.
Department of Medical-surgical Sciences and Translational Medicine, University of Rome, La Sapienza, Rome 00185, Italy.
Cancers (Basel). 2018 Jan 19;10(1):23. doi: 10.3390/cancers10010023.
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer. Single-agent mTOR targeting, mostly using rapalogs, has so far met limited clinical success; however, due to the extensive cross-talk between mTOR and other pathways, combined approaches are the most promising avenues to improve clinical efficacy of available therapeutics and overcome drug resistance. This review provides a brief and up-to-date narrative on the regulation of mTOR function, the relative contributions of mTORC1 and mTORC2 complexes to cancer development and progression, and prospects for mTOR inhibition as a therapeutic strategy.
哺乳动物雷帕霉素靶蛋白（mTOR）通路在感知和整合各种外源性信号以调节细胞生长和代谢方面起着至关重要的作用，无论是在生理还是病理条件下。mTOR通过两种功能和结构不同的多组分复合物mTORC1和mTORC2发挥作用，这两种复合物相互作用，并与其他信号通路的多个元件相互作用。在过去几年中，人们对mTOR的功能和调节有了许多新的认识，并且在小鼠中进行的广泛遗传和药理学研究加深了我们对mTOR功能障碍如何导致包括癌症在内的多种疾病的理解。迄今为止，主要使用雷帕霉素类似物的单药靶向mTOR治疗在临床上取得的成功有限；然而，由于mTOR与其他通路之间存在广泛的相互作用，联合治疗方法是提高现有疗法临床疗效和克服耐药性最有前景的途径。本综述简要介绍了mTOR功能调节、mTORC1和mTORC2复合物对癌症发生和进展的相对贡献，以及mTOR抑制作为一种治疗策略的前景。
