{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:28:31Z","timestamp":1786512511442,"version":"build-2736575974"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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>Immune checkpoint inhibitors (ICIs) have become standard treatment for KRAS-mutant lung adenocarcinoma, but acquired resistance inevitably develops. Tumor clonal evolution under therapeutic pressure is a key resistance mechanism. The emergence of a new oncogenic driver mutually exclusive with the original one is rare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>We report a 51-year-old female with stage IV lung adenocarcinoma harboring a KRAS G12C mutation along with TP53 and RB1 alterations. She received first-line therapy including the ICI tislelizumab in combination with chemotherapy and bevacizumab, achieving a partial response (PR) that was maintained for approximately 12 months (from April 2024 to April 2025), before subsequent disease progression was documented 26 months after treatment initiation. Upon disease progression, a repeat biopsy of the lung lesion revealed persistent adenocarcinoma histology without small-cell or squamous transformation. Remarkably, next-generation sequencing demonstrated the loss of the original KRAS G12C mutation and the emergence of a novel EML4-ALK fusion. The patient was switched to the ALK inhibitor ensartinib, achieving a second PR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case provides supporting evidence consistent with the selection of a pre-existing ALK fusion clone in a KRAS-mutant lung adenocarcinoma under chemo-immunotherapy pressure. It also highlights the clinical value of re-biopsy at progression to guide subsequent targeted therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1929194","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:46:13Z","timestamp":1786509973000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution from KRAS G12C-mutant to ALK fusion-positive stage IV lung adenocarcinoma following immune checkpoint inhibitor therapy: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Feng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Oncology and Hematology, Xiangyang No.6 People\u2019s Hospital","place":["Xiangyang, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Pu","sequence":"additional","affiliation":[{"name":"Wuhan Dian Medical Laboratory Co., Ltd.","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Dian Diagnostics Group Co. Ltd.","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology, Xiangyang No.6 People\u2019s Hospital","place":["Xiangyang, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s13046-025-03519-z","article-title":"Immunotherapy resistance in non-small cell lung cancer: From mechanisms to therapeutic opportunities","volume":"44","author":"Wang","year":"2025","journal-title":"J Exp Clin Cancer Res CR"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpt.2026.02.001","article-title":"From \u201cundruggable\u201d to tractable: Therapeutic advances targeting KRAS G12C-mutant cancers and emerging resistance 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