{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:04:03Z","timestamp":1784887443611,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"ABSTRACT<\/jats:title>\n \n Epidermal growth factor receptor (\n EGFR<\/jats:italic>\n ) mutations are key oncogenic drivers in non\u2010small cell lung cancer (NSCLC). Rare and compound\n EGFR<\/jats:italic>\n mutation\u2010mediated resistance to tyrosine\u2010kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we characterized compound\n EGFR<\/jats:italic>\n mutations and elucidated mechanisms of acquired resistance to\n EGFR<\/jats:italic>\n TKIs in Chinese NSCLC patients. Using next\u2010generation sequencing (NGS) data, the mutation spectrum of 10 lung cancer\u2010related genes was analyzed in 8849 patients. From this cohort, 7081 NSCLC tissue samples were assessed, revealing common\n EGFR<\/jats:italic>\n mutations (19\u2010Del, exon 21 p.L858R), rare\n EGFR<\/jats:italic>\n mutations, variants of uncertain significance (VUSs), and compound\n EGFR<\/jats:italic>\n mutations. Acquired resistance mutations were further evaluated in 77 paired baseline and post\u2010progression samples. Among the 8849 patients, 4320 (48.82%) harbored common\n EGFR<\/jats:italic>\n mutations, 973 (11.00%) carried Kirsten rat sarcoma viral oncogene (\n KRAS<\/jats:italic>\n ) hotspot mutations, 357 (4.03%) had phosphatidylinositol\u20104,5\u2010bisphosphate 3\u2010kinase catalytic subunit alpha (\n PIK3CA<\/jats:italic>\n ) mutations, 246 (2.78%) had Erb\u2010B2 receptor tyrosine kinase 2 (\n ERBB2<\/jats:italic>\n ) mutations, 102 (1.15%) had B\u2010Raf proto\u2010oncogene, serine\/threonine kinase (\n BRAF<\/jats:italic>\n ) V600E mutations, and 95 (1.07%) had mesenchymal epithelial transition factor (\n MET<\/jats:italic>\n ) mutations. Compound\n EGFR<\/jats:italic>\n mutations were identified in 7.99% of NSCLC patients, comprising 7.50% dual mutations and 0.49% multiple (>\u20092) mutations. Compared to single\n EGFR<\/jats:italic>\n mutations, compound\n EGFR<\/jats:italic>\n mutations were more frequently associated with\n EGFR<\/jats:italic>\n exon 21 p.L858R and\n EGFR<\/jats:italic>\n rare mutations, but not with\n EGFR<\/jats:italic>\n 19\u2010Del or VUSs (\n p<\/jats:italic>\n \u2009<\u20090.001). Compared to patients with\n EGFR<\/jats:italic>\n 19\u2010Del, patients with\n EGFR<\/jats:italic>\n exon 21 p.L858R mutation had significantly more rare point mutations in\n EGFR<\/jats:italic>\n exon 7, 18, and 21, and fewer\n EGFR<\/jats:italic>\n exon 20 p.T790M mutations. Additionally,\n EGFR<\/jats:italic>\n exon 20 p.T790M\u2010mediated acquired resistance was the most common mechanism (71.43%), followed by mutations in the RAS\/RAF\/MEK pathway (18.18%). These resistance\u2010associated mutations frequently co\u2010occurred with tumor protein p53 (\n TP53<\/jats:italic>\n ) variants (15.58%). Notably, the mean duration of disease progression following\n EGFR<\/jats:italic>\n \u2010TKI initiation did not differ significantly between patients with\n EGFR<\/jats:italic>\n exon 21 p.L858R mutation and those with\n EGFR<\/jats:italic>\n 19\u2010Del. Our study reveals the heterogeneity of compound\n EGFR<\/jats:italic>\n mutations, and characterizes the spectrum of acquired resistance mutations to\n EGFR<\/jats:italic>\n TKIs.\n <\/jats:p>","DOI":"10.1002\/ijc.70545","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:35:00Z","timestamp":1780547700000},"page":"1556-1565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Landscape of Chinese Lung Cancer Patients With Compound Mutations and Acquired Resistance Alterations: A Retrospective Study"],"prefix":"10.1002","volume":"159","author":[{"given":"Min","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Respiration Yellow River Sanmenxia Hospital Affiliated to Henan University of Science and Technology Sanmenxia Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology II Hebei Port Group Co., Ltd, Qinhuangdao Hospital of Integrated Traditional Chinese and Western Medicine Qinhuangdao, Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6885-571X","authenticated-orcid":false,"given":"Pei","family":"Peng","sequence":"additional","affiliation":[{"name":"Shanghai Biotecan Pharmaceuticals Co., Ltd Shanghai China"},{"name":"Shanghai Biotecan Medical Laboratory Co., Ltd Shanghai China"},{"name":"Shanghai Zhangjiang Institute of Medical Innovation Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Biotecan Pharmaceuticals Co., Ltd Shanghai China"},{"name":"Shanghai Biotecan Medical Laboratory Co., Ltd Shanghai 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