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This review synthesizes current evidence on the molecular alterations underlying SGNs and highlights emerging therapeutic targets with translational potential. A comprehensive literature search was conducted across PubMed, Google Scholar, Cochrane, and SCOPUS for studies published between 1990 and 2025, focusing on genetic aberrations, oncogenic fusions, and targeted treatment strategies. Data reveal that small molecule inhibitors and other targeted agents may offer promising alternatives to conventional chemotherapy. For instance, pleomorphic adenomas often have PLAG1 overexpression and FGFR1 fusions, activating the IGF and WNT signaling pathways; linsitinib, a dual IGF1R and tyrosine kinase inhibitor, has demonstrated antitumor activity in other malignancies and may hold potential in this context. Similarly, alterations in EGFR, HER2, and PI3K pathways across multiple salivary tumor subtypes highlight opportunities for small molecular inhibitor therapy. However, current data remain limited, and therapeutic applications are largely extrapolated from other cancers. Further research is needed to validate these findings in clinical trials. Overall, integrating molecular diagnostics with pathway-specific targeted therapies may enhance outcomes and expand treatment options for patients with SGNs.<\/jats:p>","DOI":"10.1177\/00368504261430040","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:16:59Z","timestamp":1789525019000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic alterations and targeted therapies in salivary gland neoplasms"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1396-0090","authenticated-orcid":false,"given":"Sharwani","family":"Kota","sequence":"first","affiliation":[{"name":"Robert Wood Johnson Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard V","family":"Smith","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0194599820932512"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29890"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4274\/MMJ.galenos.2022.63139"},{"key":"e_1_3_3_5_2","first-page":"8897541","article-title":"Cytogenomic abnormalities in 19 cases of salivary gland tumors of parotid gland origin","volume":"2020","author":"Zerjav M","year":"2020","unstructured":"Zerjav M, DiAdamo A, Grommisch B, et al. 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