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癌症中氧化还原失调与mTOR信号通路之间的复杂相互作用:癌症治疗的理论依据。

The complex interplay between redox dysregulation and mTOR signaling pathway in cancer: A rationale for cancer treatment.

作者信息

Glorieux Christophe, Enríquez Cinthya, Buc Calderon Pedro

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 510060 Guangzhou, China.

Química y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, 1100000 Iquique, Chile; Programa de Doctorado en Química Medicinal, Facultad de Ciencias de la Salud, Universidad Arturo Prat, 1100000 Iquique, Chile.

出版信息

Biochem Pharmacol. 2025 Feb;232:116729. doi: 10.1016/j.bcp.2024.116729. Epub 2024 Dec 19.

Abstract

The mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that plays a critical role in regulating cellular processes such as growth, proliferation, and metabolism in healthy cells. Dysregulation of mTOR signaling and oxidative stress have been implicated in various diseases including cancer. This review aims to provide an overview of the current understanding of mTOR and its involvement in cell survival and the regulation of cancer cell metabolism as well as its complex interplay with reactive oxygen species (ROS). On the one hand, ROS can inhibit or activate mTOR pathway in cancer cells through various mechanisms. Conversely, mTOR signaling can induce oxidative stress in tumor cells notably due to the inhibition in the expression of antioxidant enzyme genes. Since mTOR is often activated and plays crucial role in cancer cell survival, the use of mTOR inhibitors, which often induce ROS accumulation, could be an interesting approach for cancer treatment. This review will address the advantages, disadvantages, combination strategies, and limitations associated with therapeutic modulation of mTOR signaling pathway in cancer treatment.

摘要

雷帕霉素的作用机制靶点(mTOR)是一种高度保守的丝氨酸/苏氨酸激酶,在调节健康细胞的生长、增殖和代谢等细胞过程中发挥关键作用。mTOR信号失调和氧化应激与包括癌症在内的多种疾病有关。本综述旨在概述目前对mTOR的理解,及其在细胞存活、癌细胞代谢调节中的作用,以及它与活性氧(ROS)的复杂相互作用。一方面,ROS可通过多种机制抑制或激活癌细胞中的mTOR通路。相反,mTOR信号可显著诱导肿瘤细胞中的氧化应激,这主要是由于抗氧化酶基因表达受到抑制。由于mTOR在癌细胞存活中常被激活并发挥关键作用,使用常诱导ROS积累的mTOR抑制剂可能是一种有趣的癌症治疗方法。本综述将阐述与癌症治疗中mTOR信号通路治疗性调节相关的优点、缺点、联合策略及局限性。

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