{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:06:39Z","timestamp":1791331599056,"version":"4.3.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kaplan Cancer Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NUT midline carcinoma is a rare malignancy most commonly seen in adolescents and young adults. The disease presents most often in the lung or head and neck area but can be seen occasionally elsewhere. The diagnosis can be difficult and requires a high degree of suspicion with demonstration of the classic fusion rearrangement mutation of the NUTM1 gene with one of a variety of partners by immunohistochemistry, fluorescent in situ hybridization, or genomic analysis. Survival is usually only a number of months with few long-term survivors. Here we report one of the longest-known survivors of this disease treated with surgery and radiation without additional therapy. Systemic treatment approaches including the use of chemotherapy and BET and histone deacetylase inhibitors have yielded modest results. Further studies of these, as well as p300 and CDK9 inhibitors and combinations of BET inhibitors with chemotherapy or CDK 4\/6 inhibitors, are being evaluated. Recent reports suggest there may be a role for immune checkpoint inhibitors, even in the absence of high tumor mutation burden or PD-L1 positivity. RNA sequencing of this patient\u2019s tumor demonstrated overexpression of multiple potentially targetable genes. Given the altered transcription that results from the causative mutation multi-omic evaluation of these tumors may uncover druggable targets for treatment.<\/jats:p>","DOI":"10.1093\/oncolo\/oyad177","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T18:04:38Z","timestamp":1686679478000},"page":"765-770","source":"Crossref","is-referenced-by-count":12,"title":["Prolonged Survival of NUT Midline Carcinoma and Current Approaches to Treatment"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-5200","authenticated-orcid":false,"given":"Henry G","family":"Kaplan","sequence":"first","affiliation":[{"name":"Medical Oncology, Swedish Cancer Institute , Seattle, WA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somasundaram","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Medical Oncology, Swedish Cancer Institute , Seattle, WA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Valli\u00e8res","sequence":"additional","affiliation":[{"name":"Medical Oncology, Swedish Cancer Institute , Seattle, WA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Barnett","sequence":"additional","affiliation":[{"name":"Medical Oncology, Swedish Cancer Institute , Seattle, WA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"issue":"8","key":"2023090805133285000_CIT0001","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/s41388-020-01625-0","article-title":"Supercharging BRD4 with NUT in Carcinoma","volume":"40","author":"Eagen","year":"2021","journal-title":"Oncogene"},{"issue":"2","key":"2023090805133285000_CIT0002","doi-asserted-by":"crossref","first-page":"pkz094","DOI":"10.1093\/jncics\/pkz094","article-title":"An anatomical site and genetic-based prognostic model for patients with nuclear protein in testis (NUT) midline carcinoma: analysis of 124 patients","volume":"4","author":"Chau","year":"2019","journal-title":"JNCI Can Spect"},{"issue":"20","key":"2023090805133285000_CIT0003","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1158\/1078-0432.CCR-12-1153","article-title":"Clinicopathologic features and long-term outcomes of NUT midline carcinoma","volume":"18","author":"Bauer","year":"2012","journal-title":"Clin Can Res"},{"key":"2023090805133285000_CIT0004","doi-asserted-by":"crossref","first-page":"860830","DOI":"10.3389\/fonc.2022.860830","article-title":"NUT carcinoma: Clinicopathologic features, molecular genetics and epigenetics","volume":"12","author":"Moreno","year":"2022","journal-title":"Front Oncol."},{"issue":"7","key":"2023090805133285000_CIT0005","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1158\/0008-5472.CAN-10-3513","article-title":"Differentiation of NUT midline carcinoma by epigenomic reprogramming","volume":"71","author":"Schwartz","year":"2011","journal-title":"Can Res"},{"issue":"11","key":"2023090805133285000_CIT0006","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/pin.12727","article-title":"NUT carcinoma: Clinicopathologic features, pathogenesis, and treatment","volume":"68","author":"French","year":"2018","journal-title":"Pathol Intl"},{"issue":"5","key":"2023090805133285000_CIT0007","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00428-020-02869-7","article-title":"NUT midline carcinomas and their differentials by a single molecular profiling method: a new promising diagnostic strategy illustrated by a case report","volume":"478","author":"Haefliger","year":"2021","journal-title":"Virchows Arch."},{"issue":"7","key":"2023090805133285000_CIT0008","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1097\/PAS.0b013e318198d666","article-title":"Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody","volume":"33","author":"Haack","year":"2009","journal-title":"Am J Surg Pathol."},{"issue":"6","key":"2023090805133285000_CIT0009","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1136\/jcp.2007.052902","article-title":"Demystified molecular pathology of NUT midline carcinomas","volume":"63","author":"French","year":"2010","journal-title":"J Clin Pathol."},{"key":"2023090805133285000_CIT0010","doi-asserted-by":"crossref","first-page":"700781","DOI":"10.3389\/fonc.2021.700781","article-title":"Case report and literature review: primary pulmonary NUT-midline carcinoma","volume":"11","author":"Zhang","year":"2021","journal-title":"Front Oncol."},{"issue":"23","key":"2023090805133285000_CIT0011","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1002\/cncr.30242","article-title":"Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck","volume":"122","author":"Chau","year":"2016","journal-title":"Cancer."},{"issue":"5","key":"2023090805133285000_CIT0012","doi-asserted-by":"crossref","first-page":"e707","DOI":"10.1097\/MPH.0000000000001865","article-title":"NUT carcinoma without upfront surgical resection: a case report","volume":"43","author":"Leeman","year":"2021","journal-title":"J Pediatr Hematol Oncol."},{"issue":"3","key":"2023090805133285000_CIT0013","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00405-018-4882-y","article-title":"Patterns of care and impact of prognostic factors in the outcome of NUT midline carcinoma: a systematic review and individual patient data analysis of 119 cases","volume":"275","author":"Giridhar","year":"2018","journal-title":"Eur Arch Oto-Rhino-Laryngo"},{"issue":"5","key":"2023090805133285000_CIT0014","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/bjc.2014.54","article-title":"Comparative drug screening in NUT midline carcinoma","volume":"110","author":"Beesley","year":"2014","journal-title":"Br J Can"},{"key":"2023090805133285000_CIT0015","doi-asserted-by":"crossref","first-page":"424","DOI":"10.12659\/AJCR.893879","article-title":"Impressive response to dose-dense chemotherapy in a patient with NUT midline carcinoma","volume":"16","author":"Maur","year":"2015","journal-title":"Am J Case Rep."},{"issue":"10","key":"2023090805133285000_CIT0016","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.3390\/curroncol29100536","article-title":"Diagnosis, treatment and prognosis of primary pulmonary NUT carcinoma: a literature review","volume":"29","author":"Yuan","year":"2022","journal-title":"Curr Oncol."},{"issue":"1","key":"2023090805133285000_CIT0017","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1186\/s12885-018-5087-x","article-title":"NUT carcinoma of the nasal cavity that responded to a chemotherapy regimen for Ewing\u2019s sarcoma family of tumors: a case report","volume":"18","author":"Arimizu","year":"2018","journal-title":"BMC Cancer."},{"issue":"1","key":"2023090805133285000_CIT0018","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1097\/MPH.0000000000001860","article-title":"Metastatic NUT midline carcinoma treated with aggressive neoadjuvant chemotherapy, radiation, and resection: a case report and review of the literature","volume":"43","author":"Sopfe","year":"2021","journal-title":"J Pediatr Hematol Oncol."},{"issue":"7","key":"2023090805133285000_CIT0019","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/pbc.20755","article-title":"Successful treatment of a child with t(15:19)-positive tumor","volume":"49","author":"Mertens","year":"2007","journal-title":"Peditar Blood Can."},{"issue":"4","key":"2023090805133285000_CIT0020","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/08880018.2017.1363839","article-title":"Pediatric NUT-Midline carcinoma: Therapeutic success employing a sarcoma based multimodal approach","volume":"34","author":"Storck","year":"2017","journal-title":"Pediatr Heamtol Oncol."},{"issue":"8","key":"2023090805133285000_CIT0021","doi-asserted-by":"crossref","first-page":"e476","DOI":"10.1097\/MPH.0000000000000082","article-title":"A case of NUT midline carcinoma with complete response to gemcitabine following cisplatin and docetaxel","volume":"36","author":"Ueki","year":"2014","journal-title":"J Pediatr Hematol Oncol."},{"issue":"6","key":"2023090805133285000_CIT0022","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/ijc.33861","article-title":"Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein n testis carcinoma and other cancers: Results of a phase I\/II open-label, dose escalation study","volume":"150","author":"Cousins","year":"2022","journal-title":"Int J Cancer."},{"issue":"10","key":"2023090805133285000_CIT0023","doi-asserted-by":"crossref","first-page":"6505","DOI":"10.21037\/tcr-20-1884","article-title":"Advances in the pathogenesis and treatment of nut carcinoma: a narrative review","volume":"9","author":"Wang","year":"2020","journal-title":"Transl Can Res."},{"issue":"Sept 1","key":"2023090805133285000_CIT0024","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1101\/gad.315648.118","article-title":"Genetic modifiers of the BRD4-NUT dependency of NUT midline carcinoma uncovers a synergism between BETis and CDK4\/6is","volume":"32","author":"Liao","year":"2018","journal-title":"Genes Dev."},{"issue":"11","key":"2023090805133285000_CIT0025","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1158\/1541-7786.MCR-21-0259","article-title":"Chemical screen identifies diverse and novel histone deacetylase (HDAC) inhibitors as repressors of NUT function: implications for NUT carcinoma pathogenesis and treatment","volume":"19","author":"Shiota","year":"2021","journal-title":"Mol Can Res."},{"issue":"4","key":"2023090805133285000_CIT0026","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/pbc.25350","article-title":"Histone deacetylase inhibitor for NUT midline carcinoma","volume":"62","author":"Maher","year":"2015","journal-title":"Pediatr Blood Can."},{"issue":"12","key":"2023090805133285000_CIT0027","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1016\/j.celrep.2017.08.082","article-title":"Systematic kinase inhibitor profiling identifies CDK9 as a synthetic lethal target in NUT midline carcinoma","volume":"20","author":"Br\u00e4gelmann","year":"2017","journal-title":"Cell Rep"},{"issue":"27","key":"2023090805133285000_CIT0028","doi-asserted-by":"crossref","first-page":"e5353","DOI":"10.1073\/pnas.1703071114","article-title":"Uncovering BRD4 hyperphosphorylation associated with cellular transformation in NUT midline carcinoma","volume":"114","author":"Wang","year":"2017","journal-title":"Proc Natl Acad Sci"},{"issue":"7","key":"2023090805133285000_CIT0029","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1158\/1535-7163.MCT-20-0087","article-title":"Combined targeting of the BRD4-NUT-p300 axis in NUT midline carcinoma by dual selective bromodomain inhibitor, NEO2734","volume":"19","author":"Morrison-Smith","year":"2020","journal-title":"Mol Can Therap"},{"issue":"1","key":"2023090805133285000_CIT0030","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13023-020-01449-x","article-title":"Clinical,. features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma","volume":"15","author":"Xie","year":"2020","journal-title":"Orphanet J Rare Dis."},{"issue":"7","key":"2023090805133285000_CIT0031","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/PAI.0000000000000781","article-title":"Tumor mutation burden and checkpoint immunotherapy markers in NUT midline carcinoma","volume":"28","author":"He","year":"2020","journal-title":"Appl Immunohistochem Mol Morphol."},{"key":"2023090805133285000_CIT0032","doi-asserted-by":"crossref","first-page":"690115","DOI":"10.3389\/fonc.2021.690115","article-title":"Immunotherapy and targeting the tumor microenvironment: current place and new insights in primary pulmonary carcinoma","volume":"11","author":"Li","year":"2021","journal-title":"Front Oncol."},{"key":"2023090805133285000_CIT0033","doi-asserted-by":"crossref","first-page":"778296","DOI":"10.3389\/fonc.2021.778296","article-title":"Primary thyroid NUT carcinoma with high PD-L1 expression and Novel Massive IGKV gene fusions: a case report with treatment implications and literature review","volume":"11","author":"Zhou","year":"2022","journal-title":"Front Oncol."},{"issue":"10","key":"2023090805133285000_CIT0034","doi-asserted-by":"crossref","first-page":"101184","DOI":"10.1016\/j.tranon.2021.101184","article-title":"Genomic profiling of solid tumors harboring BRD4-NUT and response to immune checkpoint inhibitors","volume":"14","author":"Riess","year":"2021","journal-title":"Transl Oncol."},{"issue":"2","key":"2023090805133285000_CIT0035","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41588-018-0312-8","article-title":"Tumor mutational load predicts survival after immunotherapy across multiple cancer types","volume":"51","author":"Samstein","year":"2019","journal-title":"Nat Genet."},{"issue":"1","key":"2023090805133285000_CIT0036","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cell.2012.06.013","article-title":"Cancer epigenetics: from Mechanism to therapy","volume":"150","author":"Dawson","year":"2012","journal-title":"Cell."},{"issue":"10","key":"2023090805133285000_CIT0037","doi-asserted-by":"crossref","first-page":"e0163820","DOI":"10.1371\/journal.pone.0163820","article-title":"The oncoprotein BRD4-NUT generates aberrant histone modification patterns","volume":"11","author":"Zee","year":"2016","journal-title":"PLoS One."},{"key":"2023090805133285000_CIT0038","doi-asserted-by":"crossref","first-page":"700781","DOI":"10.3389\/fonc.2021.700781","article-title":"Case report and literature review: Primary pulmonary NUT-midline carcinoma","volume":"11","author":"Zhang","year":"2021","journal-title":"Front Oncol."},{"issue":"1","key":"2023090805133285000_CIT0039","first-page":"106","article-title":"SETD2 deficiency and Mir-21: Potent therapeutic targets in NUT midline carcinoma","volume":"6","author":"Yoshida","year":"2022","journal-title":"J Can Sci Clin Ther"},{"issue":"6","key":"2023090805133285000_CIT0040","first-page":"692","article-title":"NUT midline carcinoma: Morphoproteomic characterization with genomic and therapeutic correlates","volume":"45","author":"","year":"2015","journal-title":"Ann Clin Lab Sci."},{"key":"2023090805133285000_CIT0041","doi-asserted-by":"crossref","first-page":"abstract #e21008","DOI":"10.1200\/JCO.2021.39.15_suppl.e21008","article-title":"Expanding the molecular taxonomy of NUT midline carcinomas with multi-omic analyses","volume":"39","author":"Kaplan","year":"2021","journal-title":"Amer Soc Clin Oncol. J Clin Oncol"},{"issue":"1","key":"2023090805133285000_CIT0042","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4149\/neo_2018_161122N581","article-title":"Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract\u201d: a clinicopathological, immunohistochemical and molecular genetic study","volume":"65","author":"Laco","year":"2018","journal-title":"Neoplasia"},{"issue":"17","key":"2023090805133285000_CIT0043","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1002\/cam4.4096","article-title":"Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma","volume":"10","author":"Xie","year":"2021","journal-title":"Can Med."},{"issue":"1","key":"2023090805133285000_CIT0044","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13045-018-0664-7","article-title":"Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development","volume":"11","author":"Shen","year":"2018","journal-title":"J Hematol Oncol."},{"key":"2023090805133285000_CIT0045","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13000-019-0922-1","article-title":"Orbital involvement by NUT midline carcinoma: new presentation and encouraging outcome managed by radiotherapy combined with tyrosine kinase inhibitor: a case report","volume":"15","author":"Chai","year":"2020","journal-title":"Diag Pathol."},{"key":"2023090805133285000_CIT0046","first-page":"4","article-title":"NUT midline carcinoma as a primary lung tumor treated with anlotinib combined with palliative radiotherapy: a case report","volume":"17","author":"Jiang","year":"2022","journal-title":"Diag Radiol."},{"key":"2023090805133285000_CIT0047","doi-asserted-by":"crossref","first-page":"890338","DOI":"10.3389\/fonc.2022.890338","article-title":"NUT carcinoma of the lung. A case report and literature analysis","volume":"12","author":"Zhou","year":"2022","journal-title":"Front Oncol."}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/28\/9\/765\/51436951\/oyad177.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/28\/9\/765\/51436951\/oyad177.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T05:14:26Z","timestamp":1694150066000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/28\/9\/765\/7197167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,13]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,6,13]]},"published-print":{"date-parts":[[2023,9,7]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyad177","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9,1]]},"published":{"date-parts":[[2023,6,13]]}}}