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

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 w...

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Vydané v:	Molecular cancer Ročník 22; číslo 1; s. 138 - 37
Hlavní autori:	Glaviano, Antonino, Foo, Aaron S. C., Lam, Hiu Y., Yap, Kenneth C. H., Jacot, William, Jones, Robert H., Eng, Huiyan, Nair, Madhumathy G., Makvandi, Pooyan, Geoerger, Birgit, Kulke, Matthew H., Baird, Richard D., Prabhu, Jyothi S., Carbone, Daniela, Pecoraro, Camilla, Teh, Daniel B. L., Sethi, Gautam, Cavalieri, Vincenzo, Lin, Kevin H., Javidi-Sharifi, Nathalie R., Toska, Eneda, Davids, Matthew S., Brown, Jennifer R., Diana, Patrizia, Stebbing, Justin, Fruman, David A., Kumar, Alan P.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London BioMed Central 18.08.2023 BioMed Central Ltd Springer Nature B.V BMC
Predmet:	1-Phosphatidylinositol 3-kinase AKT inhibitors AKT protein Allosteric mTOR inhibitors Antineoplastic drugs Biochemistry, Molecular Biology Biomedical and Life Sciences Biomedicine Bone cancer Brain cancer Breast cancer Cancer Cancer Research Care and treatment Cell cycle Cell growth Cell survival Cellular signal transduction Cervical cancer Clinical trials Development and progression Disease resistance Dual PI3K/mTOR inhibitors Estrogens Gallbladder cancer Gastric cancer Genomics Growth factors Health aspects Humans Hyperactivity Immunotherapy Isoform-specific PI3K inhibitors Kidney cancer Kinases Leukemia Life Sciences Lung cancer Medical prognosis Melanoma Metastasis Mutation Neoplasms Neoplasms - drug therapy Neoplasms - genetics Oncology Ovarian cancer Pan PI3K inhibitors Pharmaceutical sciences Pharmacology Phosphatidylinositol 3-Kinases PI3K/AKT/mTORC pathway Prostate cancer Proto-Oncogene Proteins c-akt PTEN protein Review Sarcoma Signal Transduction Thyroid cancer TOR protein TOR Serine-Threonine Kinases Transcription factors Treatment resistance Tumors PDK1 inhibitors AKT inhibitors Pan PI3K inhibitors Allosteric mTOR inhibitors Bi-steric mTOR inhibitors PI3K/AKT/mTORC pathway Isoform-specific PI3K inhibitors Dual PI3K/mTOR inhibitors ATP-competitive mTOR inhibitors Cancer
ISSN:	1476-4598, 1476-4598
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 PMCID: PMC10436543
ISSN:	1476-4598 1476-4598
DOI:	10.1186/s12943-023-01827-6