{"id":1442,"date":"2023-08-28T02:35:28","date_gmt":"2023-08-28T02:35:28","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=1442"},"modified":"2023-08-28T02:35:28","modified_gmt":"2023-08-28T02:35:28","slug":"pi3k-akt-mtor-signaling-transduction-pathway-and-targeted-therapies-in-cancer","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/pi3k-akt-mtor-signaling-transduction-pathway-and-targeted-therapies-in-cancer\/","title":{"rendered":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer"},"content":{"rendered":"\r\n<p><strong><span style=\"font-size: 18pt;\">PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer<\/span><\/strong><\/p>\r\n<p>Antonino Glaviano1, Aaron S. C. Foo2, Hiu Y. Lam3,4, Kenneth C. H. Yap3,4, William Jacot5, Robert H. Jones6,<br \/>Huiyan Eng2,3, Madhumathy G. Nair7, Pooyan Makvandi8, Birgit Geoerger9, Matthew H. Kulke10,<br \/>Richard D. Baird11, Jyothi S. Prabhu7, Daniela Carbone1, Camilla Pecoraro1, Daniel B. L. Teh12, Gautam Sethi2,3,<br \/>Vincenzo Cavalieri1, Kevin H. Lin13, Nathalie R. Javidi\u2011Sharifi13, Eneda Toska14, Matthew S. Davids13,<br \/>Jennifer R. Brown13, Patrizia Diana1, Justin Stebbing15, David A. Fruman16 and Alan P. Kumar2,3*<\/p>\r\n<p><strong>Abstract <\/strong><\/p>\r\n<p style=\"text-align: left;\">The PI3K\/AKT\/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes<br \/>cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis<br \/>is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction<br \/>can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human<br \/>cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such<br \/>as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance<br \/>and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer,<br \/>and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic<br \/>agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance<br \/>to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.<\/p>\r\n","protected":false},"excerpt":{"rendered":"<p>PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer Antonino Glaviano1, Aaron S. C. Foo2, Hiu Y. Lam3,4, Kenneth C. H. Yap3,4, William Jacot5, Robert H. Jones6,Huiyan Eng2,3, Madhumathy G. Nair7, Pooyan Makvandi8, Birgit Geoerger9, Matthew H. Kulke10,Richard D. Baird11, Jyothi S. Prabhu7, Daniela Carbone1, Camilla Pecoraro1, Daniel B. L. Teh12, Gautam Sethi2,3,Vincenzo Cavalieri1, Kevin [&hellip;]<\/p>\n","protected":false},"author":9345,"featured_media":1443,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[5],"tags":[],"class_list":["post-1442","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer - Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/pi3k-akt-mtor-signaling-transduction-pathway-and-targeted-therapies-in-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer Antonino Glaviano1, Aaron S. C. Foo2, Hiu Y. Lam3,4, Kenneth C. H. Yap3,4, William Jacot5, Robert H. Jones6,Huiyan Eng2,3, Madhumathy G. Nair7, Pooyan Makvandi8, Birgit Geoerger9, Matthew H. Kulke10,Richard D. Baird11, Jyothi S. Prabhu7, Daniela Carbone1, Camilla Pecoraro1, Daniel B. L. 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