{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:07:07Z","timestamp":1790636827409,"version":"4.1.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Precision oncology has transformed non-small cell lung cancer (NSCLC) treatment by tailoring therapies to the genomic profile of the disease, significantly improving clinical outcomes. However, acquired resistance to molecularly targeted therapies remains a major challenge. This report details a 69-year-old woman with KRAS G12C-mutant metastatic NSCLC who developed resistance to sotorasib, a KRAS G12C inhibitor. Initially responding to the standard dose of 960\u00a0mg, the patient required a dose reduction to 480\u00a0mg due to liver toxicity. After 20 months, oligoprogression occurred, managed through surgical resection. Molecular analysis of the resected tissue identified KRAS amplification as a resistance mechanism. Following disease progression, re-escalation of sotorasib to 960\u00a0mg led to renewed tumor response without additional toxicity. This case highlights dose re-escalation as a potential strategy to address resistance in selected patients and underscores the critical role of molecular profiling and personalized approaches in optimizing targeted NSCLC treatments.<\/jats:p>","DOI":"10.1093\/oncolo\/oyaf030","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T10:04:56Z","timestamp":1742465096000},"source":"Crossref","is-referenced-by-count":3,"title":["Overcoming amplification-mediated resistance to sotorasib by dose re-escalation in <i>KRAS G12C<\/i> mutant NSCLC: a case report"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-8006","authenticated-orcid":false,"given":"Antonio","family":"Vitale","sequence":"first","affiliation":[{"name":"Comprehensive Cancer Center, Medical Oncology Department, Fondazione\u00a0Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Universita\u0300 Cattolica del Sacro Cuore , 00168 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Vita","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Medical Oncology Department, Fondazione\u00a0Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Universita\u0300 Cattolica del Sacro Cuore , 00168 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Stefani","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Medical Oncology Department, Fondazione\u00a0Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Universita\u0300 Cattolica del Sacro Cuore , 00168 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cancellieri","sequence":"additional","affiliation":[{"name":"Pathology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Lococo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, Universita\u0300 Cattolica del Sacro Cuore , 00168 Rome ,","place":["Italy"]},{"name":"Thoracic Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Tortora","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Medical Oncology Department, Fondazione\u00a0Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Universita\u0300 Cattolica del Sacro Cuore , 00168 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-704X","authenticated-orcid":false,"given":"Emilio","family":"Bria","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Medical Oncology Department, Fondazione\u00a0Policlinico Universitario Agostino Gemelli IRCCS , 00168 Rome ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Universita\u0300 Cattolica del Sacro Cuore , 00168 Rome ,","place":["Italy"]},{"name":"Medical Oncology, Ospedale Isola Tiberina \u2013 Gemelli Isola , 00186 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"2025032010032200700_CIT0001","doi-asserted-by":"publisher","first-page":"107293","DOI":"10.1016\/j.lungcan.2023.107293","article-title":"KRAS G12C in advanced NSCLC: prevalence, 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