{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:18:43Z","timestamp":1790983123776,"version":"4.1.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>c-ros oncogene 1 (ROS1) fusions occur in less than 0.2% of lung squamous cell carcinomas (SqCCs). Concurrent production of granulocyte colony-stimulating factor (G-CSF) induces marked leukocytosis and is associated with aggressive tumor behavior and resistance to conventional therapies. Here, we report a case with this rare and aggressive dual-pathology subtype response to tyrosine kinase inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 53-year-old male smoker with stage IVb SqCC (cT3N3M1) presented marked leukocytosis, and elevated serum G-CSF. The disease progressed following platinum-doublet chemotherapy and immunotherapy, despite a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or greater. Next-generation sequencing revealed an Ezrin (EZR)-ROS1 fusion. Initiation of crizotinib induced rapid partial response and leukocytosis normalization for 6 months. Sequential lorlatinib achieved sustained disease control for 10 months. Due to economic considerations, entrectinib was initiated and that maintained over 15-month ongoing response with minimal toxicity of grade 1 anemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This report suggests ROS1 fusion, G-CSF-producing lung SqCC could achieve a favorable response to molecularly-guided therapy with ROS1-tyrosine kinase inhibitors, highlighting a potential therapeutic strategy for this rare subgroup.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1933312","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:23:30Z","timestamp":1787631810000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Tyrosine kinase inhibitors in ROS1-rearranged and granulocyte colony-stimulating factor-producing lung squamous cell carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Ruijie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghe","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Henan 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