{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:02:51Z","timestamp":1779692571915,"version":"3.53.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"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":"<jats:p>\n                    Endometrial cancer is among the most commonly diagnosed malignant neoplasms of the female reproductive system, with peak incidence occurring in the perimenopausal and postmenopausal periods. The pathogenesis of this disease is multifactorial and associated with several well-established risk factors, including hormonal imbalance, obesity, and late onset of menopause. We report the case of a 64-year-old woman diagnosed with grade I endometrioid adenocarcinoma, stage IA according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patient initially underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy. More than three years after surgery, disease recurrence was detected during routine follow-up. Subsequent molecular analysis revealed a loss-of-function mutation in the\n                    <jats:italic>NF1<\/jats:italic>\n                    (neurofibromin 1) gene. Based on the molecular profile of the tumor, the patient was qualified for off-label targeted therapy with everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. Treatment with everolimus resulted in complete remission, which has been sustained to date. However, therapy was associated with significant metabolic toxicity, including severe dyslipidemia requiring pharmacological management, ultimately leading to treatment discontinuation. To our knowledge, this is the first case report to demonstrate a successful mutation-driven therapeutic decision in this specific clinical setting of endometrioid adenocarcinoma, where the identification of a pathogenic\n                    <jats:italic>NF1<\/jats:italic>\n                    loss-of-function mutation provided the only viable targeted pathway in a tumor lacking standard biomarkers such as estrogen or progesterone receptor expression or microsatellite instability. This case serves as a paradigm for mechanism-driven precision oncology, illustrating that everolimus monotherapy can achieve durable clinical benefit in\n                    <jats:italic>NF1-<\/jats:italic>\n                    deficient recurrent endometrial cancer, with remission persisting even after treatment discontinuation. These findings highlight the clinical relevance of comprehensive molecular diagnostics and support the integration of personalized treatment strategies into modern gynecologic oncology.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1828591","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:05:23Z","timestamp":1779689123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exceptional response to everolimus in an NF1-deficient recurrent endometrioid adenocarcinoma: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Maja","family":"Machulak","sequence":"first","affiliation":[{"name":"Student Scientific Society, Department of Clinical Oncology and Chemotherapy, Medical University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zwierzchowska","sequence":"additional","affiliation":[{"name":"Student Scientific Society, Department of Clinical Oncology and Chemotherapy, Medical University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"\u0141ysak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Diabetology, Copernicus Hospital","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Ko\u015bmider","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy, Medical University of Lublin","place":["Lublin, Poland"]},{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Szklener","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy, Medical University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Sk\u00f3rzewska","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology and Chemotherapy, Medical University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J 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