{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:01:26Z","timestamp":1784952086444,"version":"3.55.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MSK Support Grant","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>NRG1 fusions are unique oncogenic drivers that activate the HER3\/HER2\/PI3K pathway. The US Food and Drug Administration granted accelerated approval to a HER2\/HER3 antibody, zenocutuzumab, for treatment of NRG1 fusion-positive non\u2013small cell lung cancer and pancreatic ductal adenocarcinoma (PDAC). The optimal detection methods and clinicopathological features of patients with NRG1 fusion-positive cancer have not been systematically studied. Here, we review NRG1 fusion-positive cancer and focus on outcomes in PDAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with NRG1 fusion-positive disease at Memorial Sloan Kettering Cancer Center were identified using institutional databases. Clinicopathological data were extracted from medical records. NRG1 fusion-positive PDAC cases underwent review of radiology, pathology, treatment data, and assessment of progression-free and overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 76\u2009531 patients, 48 NRG1 fusion-positive cases were identified. The most common tumor types were lung (60%), PDAC (21%), and breast (10%). Approximately half (46%) of these patients received HER2- and\/or HER3-directed therapy. Patients were identified by RNA (n\u2009=\u200934), DNA (n\u2009=\u200911), or both (n\u2009=\u20093). RNA was superior to DNA for fusion identification. Twenty-one fusion partners were detected, most commonly CD74 (40%) and ATP1B1 (10%). Lung cancers were otherwise driver negative, and PDAC cases were KRAS wild type. NRG1 fusion-positive PDAC exhibited distinct histopathological and clinical features. Median patient age was 48.5\u2009years, median progression-free survival on first-line chemotherapy was 12.6\u2009months (n\u2009=\u20097; 95% confidence interval [CI]\u2009=\u20092.9 to not reached), and median overall survival from diagnosis was 39.6\u2009months (n\u2009=\u20099; 95% CI\u2009=\u200923.2 to not reached).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NRG1 fusions are a newly described, clinically actionable target in solid tumors. We report the landscape of NRG1 fusion-positive cancers and highlight the importance of RNA testing. NRG1 fusion-positive PDAC is enriched in younger patients with KRAS wild-type disease and has unique biology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djaf361","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:52:54Z","timestamp":1765025574000},"page":"847-855","source":"Crossref","is-referenced-by-count":2,"title":["<i>NRG1<\/i>\n                    fusion-positive solid tumors: clinical detection, genomic landscape, and real-world data in pancreatic cancer"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6070-2413","authenticated-orcid":false,"given":"Alison M","family":"Schram","sequence":"first","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-502X","authenticated-orcid":false,"given":"Soo-Ryum","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0483-7913","authenticated-orcid":false,"given":"Genessa","family":"Kahn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]},{"name":"Hunter College , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-9623","authenticated-orcid":false,"given":"Rogelio","family":"Velasco","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Lung Center of the Philippines , Quezon City 1100,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Repetto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-0310","authenticated-orcid":false,"given":"Richard","family":"Kinh Gian Do","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"DiNapoli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purvil","family":"Sukhadia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8226-6049","authenticated-orcid":false,"given":"Megan","family":"Troxel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-4794","authenticated-orcid":false,"given":"Kerem","family":"Ozcan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5046-7536","authenticated-orcid":false,"given":"Zeynep","family":"Tarcan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9055-7213","authenticated-orcid":false,"given":"Marc","family":"Ladanyi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7029-4310","authenticated-orcid":false,"given":"James J","family":"Harding","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-9061","authenticated-orcid":false,"given":"Alexander","family":"Drilon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2747-1366","authenticated-orcid":false,"given":"Olca","family":"Basturk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-9199","authenticated-orcid":false,"given":"Eileen M","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, 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