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PI3K/Akt/mTOR信号通路:在食管鳞状细胞癌中的作用、调控机制及靶向治疗机会

PI3K/Akt/mTOR Signaling Pathway: Role in Esophageal Squamous Cell Carcinoma, Regulatory Mechanisms and Opportunities for Targeted Therapy.

作者信息

Luo Qian, Du Ruijuan, Liu Wenting, Huang Guojing, Dong Zigang, Li Xiang

机构信息

Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.

出版信息

Front Oncol. 2022 Mar 22;12:852383. doi: 10.3389/fonc.2022.852383. eCollection 2022.

Abstract

Esophageal squamous cell carcinoma (ESCC), is the most common type of esophageal cancer worldwide, mainly occurring in the Asian esophageal cancer belt, including northern China, Iran, and parts of Africa. Phosphatidlinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is one of the most important cellular signaling pathways, which plays a crucial role in the regulation of cell growth, differentiation, migration, metabolism and proliferation. In addition, mutations in some molecules of PI3K/Akt/mTOR pathway are closely associated with survival and prognosis in ESCC patients. A large number of studies have found that there are many molecules in ESCC that can regulate the PI3K/Akt/mTOR pathway. Overexpression of these molecules often causes aberrant activation of PI3K/Akt/mTOR pathway. Currently, several effective PI3K/Akt/mTOR pathway inhibitors have been developed, which can play anticancer roles either alone or in combination with other inhibitors. This review mainly introduces the general situation of ESCC, the composition and function of PI3K/Akt/mTOR pathway, and regulatory factors that interact with PI3K/Akt/mTOR signaling pathway. Meanwhile, mutations and inhibitors of PI3K/Akt/mTOR pathway in ESCC are also elucidated.

摘要

食管鳞状细胞癌(ESCC)是全球最常见的食管癌类型,主要发生在亚洲食管癌高发带,包括中国北方、伊朗和非洲部分地区。磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路是最重要的细胞信号通路之一,在细胞生长、分化、迁移、代谢和增殖的调控中发挥着关键作用。此外,PI3K/Akt/mTOR通路中一些分子的突变与ESCC患者的生存和预后密切相关。大量研究发现,ESCC中有许多分子可调节PI3K/Akt/mTOR通路。这些分子的过表达常导致PI3K/Akt/mTOR通路异常激活。目前,已开发出几种有效的PI3K/Akt/mTOR通路抑制剂,它们单独或与其他抑制剂联合使用均可发挥抗癌作用。本综述主要介绍ESCC的概况、PI3K/Akt/mTOR通路的组成和功能,以及与PI3K/Akt/mTOR信号通路相互作用的调节因子。同时,也阐述了ESCC中PI3K/Akt/mTOR通路的突变和抑制剂情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61c/8980269/c21e1b1453d6/fonc-12-852383-g001.jpg

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