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Recent advances in molecular genetics have identified key mutations and signaling pathway aberrations, particularly in the PI3K\/AKT\/mTOR axis, as critical contributors to the etiology of vascular malformations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>The PI3K\/AKT\/mTOR axis regulates essential endothelial cell processes, including proliferation, migration, and metabolism. Aberrant activation of this pathway is strongly linked to slow-flow vascular malformations and PIK3CA-related overgrowth spectrum, and increasing evidence also implicates it in fast-flow vascular malformations. These findings underscore the pathway as a promising therapeutic target. This review summarizes current mechanistic insights into PI3K\/AKT\/mTOR signaling in vascular malformations and examines the therapeutic potential of targeted inhibitors. By integrating results from clinical trials with emerging molecular research, it aims to guide clinical practice while providing future directions for translational investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Recognition of PI3K\/AKT\/mTOR dysregulation provides a rationale for pathway-directed treatment. Development of selective agents and rational combination strategies\u2014guided by molecular profiling and validated in preclinical and clinical studies\u2014will be essential to enhance efficacy while minimizing resistance and toxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04115-2","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:23:20Z","timestamp":1766413400000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["PI3K\/AKT\/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials"],"prefix":"10.1186","volume":"20","author":[{"given":"Yuan-Yang","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4868-9308","authenticated-orcid":false,"given":"Chen","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"4115_CR1","doi-asserted-by":"crossref","unstructured":"Van Damme A, Seront E, Dekeuleneer V, Boon LM, Vikkula M. 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