{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021396519070336.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1186/s12943-023-01827-6"}},{"identifier":{"@type":"URI","@value":"https://link.springer.com/content/pdf/10.1186/s12943-023-01827-6.pdf"}},{"identifier":{"@type":"URI","@value":"https://link.springer.com/article/10.1186/s12943-023-01827-6/fulltext.html"}}],"dc:title":[{"@value":"PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>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. </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021396519070358","@type":"Researcher","foaf:name":[{"@value":"Antonino Glaviano"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070357","@type":"Researcher","foaf:name":[{"@value":"Aaron S. C. Foo"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070343","@type":"Researcher","foaf:name":[{"@value":"Hiu Y. Lam"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070353","@type":"Researcher","foaf:name":[{"@value":"Kenneth C. H. Yap"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070338","@type":"Researcher","foaf:name":[{"@value":"William Jacot"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070341","@type":"Researcher","foaf:name":[{"@value":"Robert H. Jones"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070347","@type":"Researcher","foaf:name":[{"@value":"Huiyan Eng"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070361","@type":"Researcher","foaf:name":[{"@value":"Madhumathy G. Nair"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070346","@type":"Researcher","foaf:name":[{"@value":"Pooyan Makvandi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070355","@type":"Researcher","foaf:name":[{"@value":"Birgit Geoerger"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070337","@type":"Researcher","foaf:name":[{"@value":"Matthew H. Kulke"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070348","@type":"Researcher","foaf:name":[{"@value":"Richard D. Baird"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070359","@type":"Researcher","foaf:name":[{"@value":"Jyothi S. Prabhu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070340","@type":"Researcher","foaf:name":[{"@value":"Daniela Carbone"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070339","@type":"Researcher","foaf:name":[{"@value":"Camilla Pecoraro"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070351","@type":"Researcher","foaf:name":[{"@value":"Daniel B. L. Teh"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070352","@type":"Researcher","foaf:name":[{"@value":"Gautam Sethi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070360","@type":"Researcher","foaf:name":[{"@value":"Vincenzo Cavalieri"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070350","@type":"Researcher","foaf:name":[{"@value":"Kevin H. Lin"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070336","@type":"Researcher","foaf:name":[{"@value":"Nathalie R. Javidi-Sharifi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070345","@type":"Researcher","foaf:name":[{"@value":"Eneda Toska"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070349","@type":"Researcher","foaf:name":[{"@value":"Matthew S. Davids"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070354","@type":"Researcher","foaf:name":[{"@value":"Jennifer R. Brown"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070342","@type":"Researcher","foaf:name":[{"@value":"Patrizia Diana"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070362","@type":"Researcher","foaf:name":[{"@value":"Justin Stebbing"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070344","@type":"Researcher","foaf:name":[{"@value":"David A. Fruman"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021396519070356","@type":"Researcher","foaf:name":[{"@value":"Alan P. Kumar"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14764598"}],"prism:publicationName":[{"@value":"Molecular Cancer"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2023-08-18","prism:volume":"22","prism:number":"1","prism:startingPage":"138"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://link.springer.com/content/pdf/10.1186/s12943-023-01827-6.pdf"},{"@id":"https://link.springer.com/article/10.1186/s12943-023-01827-6/fulltext.html"}],"createdAt":"2023-08-18","modifiedAt":"2023-11-22","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360306906068416256","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380618720896","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of Inhibitors of the Disease-Associated Protein Phosphatase Scp1 Using Antibody Mimetic Molecules"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588381049896192","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Molecular classification of ovarian high-grade serous/endometrioid carcinomas through multi-omics analysis: JGOG3025-TR2 study"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865815692847488","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Transcriptome analysis of an AKT inhibitor-resistant endometrial cancer cell line"}]},{"@id":"https://cir.nii.ac.jp/crid/1390866882736998400","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"FR429 from <i>Polygonum capitatum</i> Demonstrates Potential as an Anti-hepatic Injury Agent by Modulating PI3K/Akt Signaling Pathway"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1186/s12943-023-01827-6"},{"@type":"CROSSREF","@value":"10.1248/bpb.b24-00812_references_DOI_QVD5U6KorjzCSQfRHPXfGxZUje"},{"@type":"CROSSREF","@value":"10.1016/j.bneo.2024.100015_references_DOI_QVD5U6KorjzCSQfRHPXfGxZUje"},{"@type":"CROSSREF","@value":"10.3390/ijms25073737_references_DOI_QVD5U6KorjzCSQfRHPXfGxZUje"},{"@type":"CROSSREF","@value":"10.1038/s41416-024-02837-x_references_DOI_QVD5U6KorjzCSQfRHPXfGxZUje"},{"@type":"CROSSREF","@value":"10.1007/s43440-024-00581-w_references_DOI_QVD5U6KorjzCSQfRHPXfGxZUje"}]}