Judicious Toggling of mTOR Activity to Combat Insulin Resistance and Cancer: Current Evidence and Perspectives.
Judicious Toggling of mTOR Activity to Combat Insulin Resistance and Cancer: Current Evidence and Perspectives.
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明智地切换MTOR活动以打击胰岛素抵抗和癌症：当前的证据和观点。
DOI：
10.3389/fphar.2016.00395
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发表时间：
2016
影响因子：
5.6
通讯作者：
Sethi G
中科院分区：
文献类型：
--
作者：
Ong PS;Wang LZ;Dai X;Tseng SH;Loo SJ;Sethi G
雷帕霉素（mTOR）的机制靶点，通过其两种不同的多蛋白复合物，mTORC1和mTORC2，在细胞生长、代谢和迁移的调节中起核心作用。mTOR通路的失调反过来又与胰岛素抵抗和癌症等多种病理状况有关。据报道，mTORC1的过度激活和mTORC2功能的破坏可诱导胰岛素抵抗。另一方面，异常的mTORC1和mTORC2信号通过基因改变或mTOR及其下游靶点调节蛋白的表达增加而促进癌症的发展。这些都强调了mTOR作为克服胰岛素抵抗和癌症的治疗靶点的吸引力。这篇综述总结了支持间歇性、低剂量雷帕霉素治疗胰岛素抵抗的证据。它进一步强调了最近关于持续使用高剂量雷帕霉素类似物和相关第二代mTOR抑制剂用于根除癌症、克服化疗耐药和肿瘤干细胞抑制的数据。在这些背景下，还讨论了与使用mTOR抑制剂相关的潜在挑战。
The mechanistic target of rapamycin (mTOR), via its two distinct multiprotein complexes, mTORC1, and mTORC2, plays a central role in the regulation of cellular growth, metabolism, and migration. A dysregulation of the mTOR pathway has in turn been implicated in several pathological conditions including insulin resistance and cancer. Overactivation of mTORC1 and disruption of mTORC2 function have been reported to induce insulin resistance. On the other hand, aberrant mTORC1 and mTORC2 signaling via either genetic alterations or increased expression of proteins regulating mTOR and its downstream targets have contributed to cancer development. These underlined the attractiveness of mTOR as a therapeutic target to overcome both insulin resistance and cancer. This review summarizes the evidence supporting the notion of intermittent, low dose rapamycin for treating insulin resistance. It further highlights recent data on the continuous use of high dose rapamycin analogs and related second generation mTOR inhibitors for cancer eradication, for overcoming chemoresistance and for tumor stem cell suppression. Within these contexts, the potential challenges associated with the use of mTOR inhibitors are also discussed.
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影响因子：
168.9
作者：
Bissler, John J.;Kingswood, J. Christopher;Budde, Klemens
通讯作者：
Budde, Klemens
影响因子：
45.3
作者：
Atkins, MB;Hidalgo, M;Sherman, ML
通讯作者：
Sherman, ML
影响因子：
5.7
作者：
Bhagwat, Shripad V.;Gokhale, Prafulla C.;Pachter, Jonathan A.
通讯作者：
Pachter, Jonathan A.
影响因子：
29
作者：
Blättler SM;Cunningham JT;Verdeguer F;Chim H;Haas W;Liu H;Romanino K;Rüegg MA;Gygi SP;Shi Y;Puigserver P
通讯作者：
Puigserver P
影响因子：
6.2
作者：
Bendell JC;Kelley RK;Shih KC;Grabowsky JA;Bergsland E;Jones S;Martin T;Infante JR;Mischel PS;Matsutani T;Xu S;Wong L;Liu Y;Wu X;Mortensen DS;Chopra R;Hege K;Munster PN
通讯作者：
Munster PN