{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:12:20Z","timestamp":1779214340832,"version":"3.51.4"},"reference-count":20,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"\n Cutaneous melanoma (CM) is known for its aggressive behavior, high metastatic potential, and poor prognosis. Mutations in the\n BRAF<\/jats:italic>\n gene are common in CM, and patients with BRAF-mutant melanoma often respond well to combined inhibition of BRAF and MEK (BRAFi + MEKi). Although BRAFi + MEKi therapy provides clinical efficacy, the response durability is limited by persistent drug-tolerant residual cells, culminating in relapse. In this issue of the\n JCI<\/jats:italic>\n , Tiago et al. confirmed that NR2F1, a dormancy-associated transcription factor, is a key determinant of therapeutic resistance in melanoma. NR2F1 expression was elevated in transcriptomic datasets from patients with minimal residual disease, and in murine and human melanoma models, NR2F1 overexpression reduced therapeutic efficacy and suppressed tumor proliferation and invasion while sustaining mechanistic target of rapamycin complex 1 (mTORC1) transcriptional regulation of relevant genes. Combining BRAFi + MEKi with the mTORC1 inhibitor rapamycin effectively targeted these resistant melanoma cells, suggesting a potential path forward for targeting NR2F1 and mTORC1 signaling in patients with CM.\n <\/jats:p>","DOI":"10.1172\/jci197764","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T18:00:52Z","timestamp":1757959252000},"source":"Crossref","is-referenced-by-count":3,"title":["NR2F1 and mTORC1 provide the bridge between melanoma dormancy and therapeutic resistance"],"prefix":"10.1172","volume":"135","author":[{"given":"Narsimha","family":"Mamidi","sequence":"first","affiliation":[{"name":"Department of Cellular, Molecular and Genetic Medicine,"},{"name":"VCU Institute of Molecular Medicine, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swadesh K.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Cellular, Molecular and Genetic Medicine,"},{"name":"VCU Institute of Molecular Medicine, and"},{"name":"VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul B.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Cellular, Molecular and Genetic Medicine,"},{"name":"VCU Institute of Molecular Medicine, and"},{"name":"VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.14740\/wjon1349"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2022.0160"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000948"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01121-y"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2011.629187"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249730"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0222-9"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.08.013"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1498"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122601"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.025"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.341"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0088-5"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-23-0025"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28801-y"},{"issue":"7","key":"B16","first-page":"1684","article-title":"ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK)","volume":"63","author":"Aguirre-Ghiso","year":"2003","journal-title":"Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.07.017"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7170"},{"issue":"18","key":"B19","doi-asserted-by":"crossref","DOI":"10.1172\/JCI178446","article-title":"Elevated NR2F1 underlies the persistence of invasive disease after treatment of BRAF-mutant melanoma","volume":"135","author":"Tiago","year":"2025","journal-title":"J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-2217"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/197764\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:56:53Z","timestamp":1779213413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/197764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":20,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9,16]]},"published-print":{"date-parts":[[2025,9,16]]}},"alternative-id":["10.1172\/JCI197764"],"URL":"https:\/\/doi.org\/10.1172\/jci197764","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,16]]},"article-number":"e197764"}}