{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:19:28Z","timestamp":1790255968895,"version":"4.1.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972332"],"award-info":[{"award-number":["81972332"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:italic>FH<\/jats:italic>-deficient Renal Cell Carcinoma (<jats:italic>FH<\/jats:italic>-deficient RCC) are inherited tumors caused by mutations in the fumarate hydratase (<jats:italic>FH<\/jats:italic>) gene, which plays a role in the tricarboxylic acid cycle. These mutations often result in aggressive forms of renal cell carcinoma (RCC) and other tumors. Here, we present a case of <jats:italic>FH<\/jats:italic>-deficient RCC in a 43-year-old woman with a history of uterine fibroids. She exhibited a new heterozygous mutation in exon six of the <jats:italic>FH<\/jats:italic> gene (c.799_803del, c.781_796del). The patient had multiple bone metastases and small subcutaneous nodules in various areas such as the shoulders, back, and buttocks. Biopsy of a subcutaneous nodule on the right side revealed positive expression of 2-succinate-cysteine (2SC), and <jats:italic>FH<\/jats:italic> staining indicated <jats:italic>FH<\/jats:italic> expression deletion. The patient underwent treatment with a combination of erlotinib and bevacizumab, which resulted in significant efficacy with moderate side effects. This treatment combination may be recommended as a standard regimen. This case underscores the importance of genetic testing in patients with advanced renal cancer to enhance diagnostic accuracy. Furthermore, it provides insights into potential treatment approaches for <jats:italic>FH<\/jats:italic>-deficient RCC.<\/jats:p>","DOI":"10.3389\/fphar.2024.1373020","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:03:35Z","timestamp":1718946215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case report: successful response to bevacizumab combined with erlotinib for a novel FH gene mutation hereditary leiomyoma and renal cell carcinoma"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiaoming","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1158\/1078-0432.CCR-19-3323","article-title":"Targeting PD-1 or PD-L1 in metastatic kidney cancer: combination therapy in the first-line setting","volume":"26","author":"Aggen","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s40259-020-00449-4","article-title":"The immunotherapy landscape in renal cell carcinoma","volume":"34","author":"Brown","year":"2020","journal-title":"BioDrugs"},{"key":"B3","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.ejca.2021.04.009","article-title":"Response to systemic therapy in fumarate hydratase\u2013deficient renal cell carcinoma","volume":"151","author":"Carril-Ajuria","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"102017","DOI":"10.1016\/j.ctrv.2020.102017","article-title":"Bevacizumab (Avastin\u00ae) in cancer treatment: a review of 15\u00a0years of clinical experience and future outlook","volume":"86","author":"Garcia","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.7150\/thno.38346","article-title":"The combination of bevacizumab\/Avastin and erlotinib\/Tarceva is relevant for the treatment of metastatic renal cell carcinoma: the role of a synonymous mutation of the EGFR receptor","volume":"10","author":"Gr\u00e9pin","year":"2020","journal-title":"Theranostics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1080\/21645515.2019.1571892","article-title":"PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations","volume":"15","author":"Jiang","year":"2019","journal-title":"Hum. Vaccines Immunother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/PAS.0000000000001372","article-title":"A clinicopathologic and molecular analysis of fumarate hydratase-deficient renal cell carcinoma in 32 patients","volume":"44","author":"Lau","year":"2020","journal-title":"Am. J. Surg. Pathology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"906014","DOI":"10.3389\/fonc.2022.906014","article-title":"Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma","volume":"12","author":"Lindner","year":"2022","journal-title":"Front. Oncol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s41585-019-0211-5","article-title":"The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications","volume":"16","author":"Linehan","year":"2019","journal-title":"Nat. Rev. Urol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41591-018-0053-3","article-title":"Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma","volume":"24","author":"McDermott","year":"2018","journal-title":"Nat. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1038\/s41379-018-0017-7","article-title":"Pattern multiplicity and fumarate hydratase (FH)\/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration","volume":"31","author":"Muller","year":"2018","journal-title":"Mod. Pathol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1097\/PAS.0000000000001000","article-title":"Reappraisal of morphologic differences between renal medullary carcinoma, collecting duct carcinoma, and fumarate hydratase\u2013deficient renal cell carcinoma","volume":"42","author":"Ohe","year":"2018","journal-title":"Am. J. Surg. Pathology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1097\/PAP.0b013e3181f89400","article-title":"The use of immunohistochemistry in the diagnosis of metastatic clear cell renal cell carcinoma: a review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10","volume":"17","author":"Sangoi","year":"2010","journal-title":"Adv. Anatomic Pathology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1002\/ijc.25397","article-title":"PD-1 and PD-L1 upregulation promotes CD8+ T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients","volume":"128","author":"Shi","year":"2011","journal-title":"Int. J. Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1097\/PAS.0000000000000719","article-title":"Tubulocystic carcinoma of the kidney with poorly differentiated foci: a frequent morphologic pattern of fumarate hydratase-deficient renal cell carcinoma","volume":"40","author":"Smith","year":"2016","journal-title":"Am. J. Surg. Pathology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1158\/1078-0432.CCR-20-3788","article-title":"Integrated molecular characterization of fumarate hydratase\u2013deficient renal cell carcinoma","volume":"27","author":"Sun","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1038\/s41416-023-02412-w","article-title":"Fumarate hydratase (FH) and cancer: a paradigm of oncometabolism","volume":"129","author":"Valcarcel-Jimenez","year":"2023","journal-title":"Br. J. Cancer"},{"key":"B18","doi-asserted-by":"publisher","first-page":"735077","DOI":"10.3389\/fonc.2021.735077","article-title":"Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-Associated renal cell carcinoma to pembrolizumab immunotherapy: a case report","volume":"11","author":"Wang","year":"2021","journal-title":"Front. Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.3389\/fonc.2020.01181","article-title":"Prognostic value of Vimentin is associated with immunosuppression in metastatic renal cell carcinoma","volume":"10","author":"Yao","year":"2020","journal-title":"Front. Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"791.e9","DOI":"10.1016\/j.urolonc.2021.07.026","article-title":"Hereditary leiomyomatosis and renal cell cancer (HLRCC): case series and review of the literature","volume":"39","author":"Yu","year":"2021","journal-title":"Urologic Oncol. Seminars Orig. Investigations"},{"key":"B21","doi-asserted-by":"publisher","first-page":"100303","DOI":"10.1016\/j.modpat.2023.100303","article-title":"AKR1B10 is a new sensitive and specific marker for fumarate hydratase-deficient renal cell carcinoma","volume":"36","author":"Zheng","year":"2023","journal-title":"Mod. Pathol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/j.ccell.2021.07.005","article-title":"Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): a multicenter phase 3 study","volume":"39","author":"Zhou","year":"2021","journal-title":"Cancer Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1136\/jclinpath-2021-207830","article-title":"Gene of the month: FH","volume":"74","author":"Zyla","year":"2021","journal-title":"J. Clin. Pathology"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1373020\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:03:38Z","timestamp":1718946218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1373020\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,21]]},"references-count":23,"alternative-id":["10.3389\/fphar.2024.1373020"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1373020","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,21]]},"article-number":"1373020"}}