{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:44:24Z","timestamp":1784126664679,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    Clinical outcomes in\n                    <jats:italic>ROS1<\/jats:italic>\n                    \u2010fusion positive (\n                    <jats:italic>ROS1<\/jats:italic>\n                    +) non\u2010small cell lung cancer (NSCLC) by fusion partner and resistance mechanisms are limited. This cohort study included 56\n                    <jats:italic>ROS1+<\/jats:italic>\n                    patients (FISH or NGS confirmed); fusion partners were identified in 27 cases, including\n                    <jats:italic>CD74<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910),\n                    <jats:italic>EZR<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097), and\n                    <jats:italic>SDC4<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097). Clinical data were available for 50 patients (median age 62; 51% female; 32% never\u2010smokers). Forty patients received tyrosine kinase inhibitors (TKIs), mostly crizotinib (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200938). Crizotinib showed a 55% objective response rate (ORR) and a median progression\u2010free survival (mPFS) of 5.3\u2009months. Brain metastases (HR 2.65, 95% CI 1.06\u20136.60,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.037) and prior chemotherapy (HR 3.17, 95% CI 1.35\u20137.45,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.008) had a higher risk of progression. Sixteen patients received subsequent lorlatinib, with an ORR of 28% and mPFS of 3.7\u2009months. G2032R and L2026M resistance mutations were identified in four lorlatinib non\u2010responders, and\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies confirmed resistance to lorlatinib. Fusion partners did not affect crizotinib outcomes. Lorlatinib was ineffective against on\u2010target resistance. Real\u2010world data showed lower TKI efficacy than clinical trials, highlighting the role of clinical and molecular factors in treatment response.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70109","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T08:41:23Z","timestamp":1756456883000},"page":"3023-3034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The influence of\n                    <i>ROS1<\/i>\n                    fusion partners and resistance mechanisms in\n                    <i>ROS1<\/i>\n                    \u2010\n                    <scp>TKI<\/scp>\n                    \u2010treated non\u2010small cell lung cancer patients"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-0105","authenticated-orcid":false,"given":"Fenneke","family":"Zwierenga","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine University of Groningen, University Medical Center Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Dijkhuizen","sequence":"additional","affiliation":[{"name":"Institute For Life Science and Technology Hanze University of Applied Sciences  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Korthuis","sequence":"additional","affiliation":[{"name":"Institute For Life Science and Technology Hanze University of Applied Sciences  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Timens","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology University of Groningen, University Medical Center Groningen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of 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