{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:12:59Z","timestamp":1790007179791,"version":"4.0.1"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Objective<\/jats:title>\n \n Primary malignant melanoma of the uterine cervix is an exceptionally rare malignancy with a biology distinct from its cutaneous counterpart and a dire prognosis. This case provides a critical\n in vivo<\/jats:italic>\n model for interrogating the therapeutic resistance mechanisms inherent to mucosal melanomas.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We report a case of a 73-year-old woman with early-stage (pT1aN0), NRAS Q61K-mutant primary cervical melanoma.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The patient progressed rapidly through radical surgery and adjuvant Toripalimab (anti-PD-1) immunotherapy. Despite salvage therapy with a MEK inhibitor, she succumbed to the disease 17 months after diagnosis. The sequential failure of both immune checkpoint blockade and targeted pathway inhibition highlights a dual-layer of resistance.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This experience mandates a fundamental re-evaluation of adjuvant strategies for this disease. It provides a compelling rationale for upfront, biology-driven combination trials (e.g., immunotherapy plus MEK or CDK4\/6 inhibition) in the neoadjuvant or adjuvant setting for high-risk cases.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1803729","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:50:37Z","timestamp":1774421437000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Primary malignant melanoma of the uterine cervix: a case report of aggressive progression despite multimodal therapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Qing","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pathology, Deyang People\u2019s Hospital","place":["Deyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.05.036","article-title":"Malignant melanoma of the cervix uteri: a population-based analysis","volume":"158","author":"Rouzbahman","year":"2020","journal-title":"Gynecol Oncol"},{"key":"B2","volume-title":"WHO Classification of Tumours: Female Genital Tumours","year":"2020"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.2789","article-title":"Long-term survival and safety in patients with advanced mucosal melanoma treated with nivolumab or nivolumab plus ipilimumab: a pooled analysis of 4 clinical trials","volume":"8","author":"Hamid","year":"2022","journal-title":"JAMA Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2020.11.056","article-title":"Primary Malignant melanoma of the uterine cervix: A comprehensive systematic review","volume":"256","author":"Mert","year":"2021","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/s41467-022-34367-2","article-title":"Evolutionary characterization of mucosal melanoma identifies distinct immune and metabolic profiles associated with immunotherapy resistance","volume":"14","author":"Rodrigues","year":"2023","journal-title":"Nat Commun"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34367-2","article-title":"Immunotherapy and radiotherapy in melanoma: A multidisciplinary comprehensive review","volume":"13","author":"Tagliaferri","year":"2023","journal-title":"J Pers Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30180-8","article-title":"Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a phase 3 trial","volume":"18","author":"Dummer","year":"2017","journal-title":"Lancet Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1450","article-title":"Combined MEK and CDK4\/6 inhibition in NRAS-mutant melanoma: a phase I\/II trial","volume":"12","author":"Yao","year":"2022","journal-title":"Cancer Discov"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e2212409120","DOI":"10.1073\/pnas.2212409120","article-title":"Combined targeting of MEK and PI3K\/mTOR effector pathways is necessary to effectively inhibit NRAS mutant melanoma","volume":"120","author":"Posch","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30445-X","article-title":"Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet","volume":"18","author":"Gatta","year":"2017","journal-title":"Lancet Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1803729\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:50:41Z","timestamp":1774421441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1803729\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":10,"alternative-id":["10.3389\/fonc.2026.1803729"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1803729","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1803729"}}