癌症中的PI3K/AKT/mTOR信号转导途径及靶向治疗。
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.
发表日期：2023 Aug 18
作者：
Antonino Glaviano, Aaron S C Foo, Hiu Y Lam, Kenneth C H Yap, William Jacot, Robert H Jones, Huiyan Eng, Madhumathy G Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H Kulke, Richard D Baird, Jyothi S Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B L Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H Lin, Nathalie R Javidi-Sharifi, Eneda Toska, Matthew S Davids, Jennifer R Brown, Patrizia Diana, Justin Stebbing, David A Fruman, Alan P Kumar
来源：
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要：
PI3K/AKT/mTOR（PAM）信号通路是真核细胞中一种高度保守的信号转导网络，促进细胞存活、细胞生长和细胞周期进程。在PAM轴中，生长因子通过多重交叉作用与其他几种信号通路严格调控转录因子的信号传导，并且信号传导的失调可能会导致癌症的发展。PAM轴是人类癌症中最常活化的信号通路，常常与抗癌治疗的耐药性有关。这一通路的组分失调，如PI3K的高活性、PTEN的失活、AKT的增益功能，是导致癌症治疗耐药性和疾病进展的臭名昭著的推动因素。本文综述了癌症中PAM信号通路的主要失调，并讨论了PI3K、AKT和mTOR抑制剂作为单药治疗以及与其他抗肿瘤药物联合治疗在临床试验中的结果，作为克服治疗耐药性的策略。最后，还讨论了PAM信号靶向治疗的主要耐药机制，包括PAM信号在免疫学和免疫疗法中的作用。©2023年 BioMed Central Ltd., Springer Nature的一部分。
The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.© 2023. BioMed Central Ltd., part of Springer Nature.