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VMs are characterized by abnormal vessel development, overgrowth, and dysfunction. Coagulopathy, edema, and effusions can cause severe morbidity and mortality in children and adults with these diseases. Germline or somatic mutations in the RAS\/RAF\/MAPK pathway have been identified in multiple types of VAs.\n                    <jats:italic>RAS<\/jats:italic>\n                    genes (\n                    <jats:italic>KRAS<\/jats:italic>\n                    ,\n                    <jats:italic>NRAS<\/jats:italic>\n                    , and\n                    <jats:italic>HRAS<\/jats:italic>\n                    ) are small GTPase proteins that play an important role in normal development and cell function. In healthy cells, RAS proteins cycle between GDP (inactive) and GTP (active) states that regulate important functions such as proliferation, migration, and survival. \u201cHot spot\u201d mutations in codons 12, 13, or 61 of\n                    <jats:italic>RAS<\/jats:italic>\n                    genes are found in multiple tumor types and VAs.\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations often cause excessive MAP kinase signaling, driving unchecked cell proliferation. In this review, we discuss the different RAS pathway mutations discovered in VAs and the role that these may play using insights from cell and animal models. Current therapies targeting RAS pathways are presented. In the future, a better understanding of the role of RAS pathway mutations may advance therapeutic strategies for people with VAs.\n                  <\/jats:p>","DOI":"10.1002\/pbc.31605","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:33:21Z","timestamp":1740170001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["RAS Pathway Mutations and Therapeutics in Vascular Anomalies"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-9592","authenticated-orcid":false,"given":"Sara","family":"Alharbi","sequence":"first","affiliation":[{"name":"Cancer and Cell Biology Program University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Pulmonary Biology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7604-3849","authenticated-orcid":false,"given":"Svatava","family":"Merkle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Pulmonary Biology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Hematology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-4924","authenticated-orcid":false,"given":"Adrienne M.","family":"Hammill","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Hematology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio 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