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Head and neck cancer (HNC) constitutes a substantial group of malignancies occurring in various anatomical regions of the head and neck, including lips, mouth, throat, larynx, nose, sinuses, oropharynx, hypopharynx, nasopharynx, and salivary glands. The present study addresses the phosphoinositide 3\u2010kinase (PI3K)\/<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/protein-kinase-b\">protein kinase B<\/jats:ext-link> (Akt)\/mammalian target of rapamycin (mTOR) pathway as a possible therapeutic target in cancer therapy. Finding new multitargeting agents capable of modulating PI3K\/Akt\/mTOR and cross\u2010linked mediators could be viewed as an effective strategy in combating HNC. Recent studies have introduced phytochemicals as multitargeting agents and rich sources for finding and developing new therapeutic agents. Phytochemicals have exhibited immense anticancer effects, including targeting different stages of HNC through the modulation of several signaling pathways. Moreover, phenolic\/polyphenolic compounds, alkaloids, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/terpene\">terpenes<\/jats:ext-link>\/<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/terpenoid\">terpenoids<\/jats:ext-link>, and other secondary metabolites have demonstrated promising <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/anticarcinogen\">anticancer<\/jats:ext-link> activities because of their diverse pharmacological and biological properties like antiproliferative, antineoplastic, antioxidant, and anti\u2010inflammatory activities. The current review is mainly focused on new therapeutic strategies for HNC passing through the PI3K\/Akt\/mTOR pathway as new strategies in combating HNC.<\/jats:p>","DOI":"10.1002\/ptr.8228","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T15:50:41Z","timestamp":1716393041000},"page":"3736-3762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exploiting new strategies in combating head and neck carcinoma: A comprehensive review on phytochemical approaches passing through <scp>PI3K<\/scp>\/Akt\/<scp>mTOR<\/scp> signaling pathway"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-6151","authenticated-orcid":false,"given":"Amin","family":"Iranpanah","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Health Institute Kermanshah University of Medical Sciences  Kermanshah 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