{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:40:32Z","timestamp":1778827232974,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>EGFR-mutant lung cancers develop a wide range of potential resistance alterations under therapy with the third-generation EGFR tyrosine kinase inhibitor osimertinib. MET amplification ranks among the most common acquired resistance alterations and is currently being investigated as a therapeutic target in several studies. Nevertheless, targeted therapy of MET might similarly result in acquired resistance by point mutations in MET, which further expands therapeutic and diagnostic challenges. Here, we report a 50-year-old male patient with EGFR-mutant lung adenocarcinoma and stepwise acquired resistance by a focal amplification of MET followed by D1246N (D1228N), D1246H (D1228H), and L1213V (L1195V) point mutations in MET, all detected by NGS. The patient successfully responded to the combined and sequential treatment of osimertinib, osimertinib\/crizotinib, and third-line osimertinib\/cabozantinib. This case highlights the importance of well-designed, sequential molecular diagnostic analyses and the personalized treatment of patients with acquired resistance.<\/jats:p>","DOI":"10.3390\/curroncol30100635","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:49:14Z","timestamp":1695786554000},"page":"8805-8814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Combined Therapy of Cabozantinib, Crizotinib, and Osimertinib in a Lung Cancer Patient with Acquired MET Amplification and Resistance Mutations"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-9526","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"J\u00f3ri","sequence":"first","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"V\u00f6ssing","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Pirngruber","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-9214","authenticated-orcid":false,"given":"Eva Maria","family":"Willing","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Arndt","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5511-9146","authenticated-orcid":false,"given":"Markus","family":"Falk","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Tiemann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas C.","family":"Heukamp","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Institut f\u00fcr H\u00e4matopathologie Hamburg, Fangdieckstra\u00dfe 75A, 22547 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Hoffknecht","sequence":"additional","affiliation":[{"name":"Lungenkrebsmedizin Oldenburg, Georgstra\u00dfe 12, 26121 Oldenburg, Germany"},{"name":"Department of Thorax Oncology, Niels-Stensen-Kliniken, Franziskus-Hospital Harderberg Alte, Rothen-Felder Stra\u00dfe 23, 49124 Georgsmarienh\u00fctte, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in untreated egfr-mutated advanced non-small-cell lung cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N. 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