{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:25:07Z","timestamp":1787729107273,"version":"build-2784847793"},"reference-count":57,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n With novel RAS-targeted therapies emerging, better understanding of RAS-driven differentiated (DTC) and anaplastic (ATC) thyroid cancers is warranted.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n Characterize the genotypic and phenotypic landscape of RAS-driven DTC and ATC and review current and future therapeutic avenues.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Retrospective chart review between January 2015 and June 2023. Median follow-up duration 8.4 years in DTC cohort and 36.4 months in ATC cohort.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n Single-center study at MD Anderson Cancer Center.<\/jats:p>\n <\/jats:sec>\n \n Patients<\/jats:title>\n Individuals with RAS-altered DTC or ATC identified before kinase inhibitor exposure.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n None.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measures<\/jats:title>\n Primary objective was to describe clinical and molecular characteristics. Secondary objectives included identifying prognostic factors and assessing survival outcomes with available therapies.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 120 RAS-driven DTC and 71 RAS-driven ATC, NRAS was the most common alteration (69% of DTC, 70% of ATC), mainly at residue Q61. Brain metastases were found in 22% of patients undergoing brain imaging (19% in DTC, 25% in ATC). Median overall survival (OS) was 15.2 years in DTC, with 49% of patients receiving at least 1 line of systemic therapy, most commonly lenvatinib (66%). Median time to systemic therapy was 3.5 years from diagnosis, and median OS from therapy initiation was 6.0 years. In ATC, median OS was 7.5 months. Stage IVC [hazard ratio (HR) = 6.78)], neck surgery (HR = 0.29), and exposure to immunotherapy (HR = 0.13) were significantly associated with mortality.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Advanced RAS-driven follicular-derived thyroid cancers seem to exhibit an aggressive behavior, particularly in ATC, in which prognosis remains poor despite expert multidisciplinary care. Advances in RAS-targeted therapies offer hope for improved therapeutic options.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf366","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:00:12Z","timestamp":1750838412000},"page":"471-483","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of Advanced\n RAS<\/i>\n -driven Follicular-derived Thyroid Cancers and Review of Future Therapeutic Avenues"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-9885","authenticated-orcid":false,"given":"Sarah","family":"Hamidi","sequence":"first","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 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