Обзорная статья

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Antonino GlavianoDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, ItalyAaron Song Chuan FooDepartment of Surgery, National University Hospital Singapore, National University of Singapore, Singapore, SingaporeHiu Yan LamDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, SingaporeKenneth Chun-Yong YapDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, SingaporeWilliam JacotDepartment of Medical Oncology, Institut du Cancer de Montpellier, Inserm U1194, Montpellier University, Montpellier, FranceRobert H. JonesCardiff University and Velindre Cancer Centre, Museum Avenue, Cardiff, CF10 3AX, UKHuiyan EngDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, SingaporeMadhumathy G NairDivision of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore, 560034, IndiaPooyan MakvandiThe Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, Zhejiang, ChinaBirgit GeoergerDepartment of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Center, Inserm U1015, Université Paris-Saclay, Paris, FranceMatthew H. KulkeSection of Hematology and Medical Oncology, Boston University and Boston Medical Center, Boston, MA, USARichard D. BairdCancer Research UK Cambridge Centre, Hills Road, Cambridge, CB2 0QQ, UKJyothi S. PrabhuDivision of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore, 560034, IndiaDaniela CarboneDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, ItalyCamilla PecoraroDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, ItalyDaniel Boon Loong TehDepartments of Ophthalmology and Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, and Neurobiology Programme, National University of Singapore, Singapore, SingaporeGautam SethiDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, SingaporeVincenzo CavalieriDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, ItalyKevin LinDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USANathalie Javidi‐SharifiDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAEneda ToskaDepartment of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, MD, USAMatthew S. DavidsDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAJennifer R. BrownDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAPatrizia DianaDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, ItalyJustin StebbingDivision of Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UKDavid A. FrumanDepartment of Molecular Biology and Biochemistry, University of California, 216 Sprague Hall, Irvine, CA, USAAlan Prem KumarDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore. [email protected]

2023en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1186/s12943-023-01827-6

Цитирования и источники

Цитирований: 4Использованных источников: 0

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