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

被引：0

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

机构：

[1] University of Palermo,Department of Biological, Chemical and Pharmaceutical Sciences and Technologies

[2] National University Hospital Singapore,Department of Surgery

[3] National University of Singapore,Department of Pharmacology, Yong Loo Lin School of Medicine

[4] National University of Singapore,NUS Centre for Cancer Research (N2CR)

[5] Yong Loo Lin School of Medicine,Department of Medical Oncology, Institut du Cancer de Montpellier, Inserm U1194

[6] National University of Singapore,Division of Molecular Medicine

[7] Montpellier University,Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Center, Inserm U1015

[8] Cardiff University and Velindre Cancer Centre,Section of Hematology and Medical Oncology

[9] St. John’s Research Institute,Departments of Ophthalmology and Anatomy

[10] St. John’s Medical College,Dana

[11] The Quzhou Affiliated Hospital of Wenzhou Medical University,Farber Cancer Institute

[12] Quzhou People’s Hospital,Department of Biochemistry and Molecular Biology

[13] Université Paris-Saclay,Division of Cancer

[14] Boston University and Boston Medical Center,Department of Molecular Biology and Biochemistry

[15] Cancer Research UK Cambridge Centre,undefined

[16] Yong Loo Lin School of Medicine,undefined

[17] National University of Singapore,undefined

[18] and Neurobiology Programme,undefined

[19] National University of Singapore,undefined

[20] Harvard Medical School,undefined

[21] Johns Hopkins School of Public Health,undefined

[22] Imperial College London,undefined

[23] Hammersmith Campus,undefined

[24] University of California,undefined

来源：

Molecular Cancer | / 22卷

关键词：

PI3K/AKT/mTORC pathway; Pan PI3K inhibitors; Isoform-specific PI3K inhibitors; Dual PI3K/mTOR inhibitors; AKT inhibitors; Allosteric mTOR inhibitors; ATP-competitive mTOR inhibitors; Bi-steric mTOR inhibitors; PDK1 inhibitors; Cancer;

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摘要：

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.

引用

共 50 条

[1] PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
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Teh, Daniel B. L.
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