mTOR Cross-Talk in Cancer and Potential for Combination Therapy.
mTOR Cross-Talk in Cancer and Potential for Combination Therapy.
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DOI：
10.3390/cancers10010023
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发表时间：
2018-01-19
期刊：
影响因子：
5.2
通讯作者：
Milella M
中科院分区：
文献类型：
--
作者：
Conciatori F;Ciuffreda L;Bazzichetto C;Falcone I;Pilotto S;Bria E;Cognetti F;Milella M
雷帕霉素靶蛋白（mTOR）通路在生理和病理条件下，在感知和整合多种外源性信号以调节细胞生长和代谢方面都起着至关重要的作用。mTOR通过两种在功能和结构上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若干元件相互作用。在过去几年中，人们对mTOR的功能和调节有了许多新的见解，并且在小鼠中进行的大量遗传学和药理学研究增进了我们对mTOR功能失调如何导致包括癌症在内的多种疾病的理解。到目前为止，主要使用雷帕霉素类似物的单一药物靶向mTOR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希望的途径。本综述简要且最新地阐述了mTOR功能的调节、mTORC1和mTORC2复合物对癌症发生和发展的相对作用，以及mTOR抑制作为一种治疗策略的前景。
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.
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影响因子：
28.2
作者：
Cheng H;Zou Y;Ross JS;Wang K;Liu X;Halmos B;Ali SM;Liu H;Verma A;Montagna C;Chachoua A;Goel S;Schwartz EL;Zhu C;Shan J;Yu Y;Gritsman K;Yelensky R;Lipson D;Otto G;Hawryluk M;Stephens PJ;Miller VA;Piperdi B;Perez-Soler R
通讯作者：
Perez-Soler R
DOI：
10.1084/jem.20081297
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Liu Y;Liu R;Ikenoue T;Guan KL;Liu Y;Zheng P
通讯作者：
Zheng P
影响因子：
--
作者：
Ciuffreda, Ludovica;Falcone, Italia;Milella, Michele
通讯作者：
Milella, Michele
影响因子：
45.3
作者：
Andre, Fabrice;Hurvitz, Sara;Slamon, Dennis
通讯作者：
Slamon, Dennis
影响因子：
16
作者：
Bakker, Walbert J.;Harris, Isaac S.;Mak, Tak W.
通讯作者：
Mak, Tak W.