{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:44:13Z","timestamp":1788194653888,"version":"build-2803163510"},"reference-count":103,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to explore the persistent activation of the PI3K\/AKT signaling pathway in various cancers, with a focus on upstream coactivators that drive tumor growth and contribute to therapeutic resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An integrated overview of four disparate tumorigenic coactivators of PI3K\/AKT signaling, namely, TMEPAI (a transmembrane adaptor protein), SALL4 (a zinc\u2010finger transcription factor), TCL1B (an oncoprotein coactivator), and TGF\u2010\u03b2 (a cytokine ligand) was identified and analyzed through a comprehensive literature review. Their mechanistic insights, signaling interactions, and therapeutic opportunities were also summarized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study outcomes demonstrate that each of these coactivators contributes to PI3K\/AKT pathway hyperactivation and cancer progression through distinct mechanisms, such as the downregulation of negative regulators or direct enhancement of AKT activation. Emerging therapeutic approaches targeting these coactivators through gene silencing, small\u2010molecule inhibitors, and peptide\u2010based interventions were also outlined, along with associated challenges such as drug specificity, toxicity, and resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By synthesizing evidence across these diverse molecules, this review highlights the convergent impact of multiple molecular classes on the PI3K\/AKT pathway and outlines future perspectives for leveraging these insights in targeted cancer therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71304","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:28:46Z","timestamp":1761805726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting Tumorigenic Coactivators in the\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Signaling Pathway: A Novel Approach for Cancer Treatment"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-4121","authenticated-orcid":false,"given":"Md. Anwarul","family":"Haque","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Science University of Rajshahi  Rajshahi Bangladesh"},{"name":"Department of Experimental Pathology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanasis","family":"Poullikkas","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"},{"name":"Department of Biochemistry and Systems Biomedicine Juntendo University Graduate School of Medicine  Tokyo Japan"},{"name":"Nakatani Biomedical Spatialomics Hub Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. M. Al\u2010Amin","family":"Kaisar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science University of Rajshahi  Rajshahi Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alam","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science University of Rajshahi  Rajshahi Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shariful","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Pabna University of Science and Technology  Pabna Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murshida","family":"Mollik","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Manarat International University  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mst. 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