{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:10Z","timestamp":1785387610487,"version":"3.55.0"},"reference-count":13,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR\u2010mutant non\u2013small\u2010cell lung cancer (NSCLC) is heterogeneous, and serial re\u2010biopsy may uncover actionable mechanisms. We report a 55\u2010year\u2010old man with stage IVB lung adenocarcinoma harboring EGFR L858R and TP53 R282W. First\u2010line icotinib produced a partial response (PR) with progression\u2010free survival (PFS) of 7\u2009months. Rebiopsy at progression identified acquired EGFR T790M together with a MET c.3010C&gt;G exon 14\u2010related alteration. Almonertinib induced a second PR lasting 7\u2009months. After renewed progression, almonertinib plus savolitinib achieved another PR for 8\u2009months, supporting MET\u2010dependent bypass resistance. Biopsy of a newly progressive iliac metastasis then showed emergence of RET\u2010CCDC6 fusion, whereas T790M and the MET alteration were no longer detected. Because selective RET inhibition was initially unaffordable, the patient received pemetrexed\u2010carboplatin plus continued almonertinib, followed by selpercatinib plus almonertinib. Local radiotherapy to oligoprogressive bone and lung lesions prolonged benefit from systemic therapy. At the latest follow\u2010up in January 2026, the patient remained alive nearly 50\u2009months after diagnosis. This case illustrates clonal evolution under treatment pressure and highlights three practical lessons: repeat molecular testing at each clinically meaningful progression, matched combination targeted therapy for actionable bypass alterations, and local ablative radiotherapy for oligoprogression.<\/jats:p>","DOI":"10.1111\/1759-7714.70322","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T02:01:09Z","timestamp":1785117669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential\n                    <scp>EGFR T790M<\/scp>\n                    ,\n                    <scp>MET<\/scp>\n                    c.\n                    <scp>3010C<\/scp>\n                    &gt;G\u2010Associated Exon 14 Alteration, and\n                    <scp>RET<\/scp>\n                    \u2010\n                    <scp>CCDC6<\/scp>\n                    Fusion in\n                    <scp>EGFR<\/scp>\n                    \u2010Mutant\n                    <scp>NSCLC<\/scp>\n                    : A Case Report"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6750-0838","authenticated-orcid":false,"given":"Yan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Oncology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9762-2559","authenticated-orcid":false,"given":"Nan\u2010Lin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Kai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology Peking University First Hospital  Beijing 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