{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:29:13Z","timestamp":1786609753902,"version":"build-2736575974"},"reference-count":11,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Circulating tumor DNA (ctDNA) monitoring may detect resistance to\n KRAS<\/jats:italic>\n G12C<\/jats:sup>\n inhibitors earlier than conventional imaging. However, in the specific context of\n KRAS<\/jats:italic>\n G12C<\/jats:sup>\n inhibitors, the temporal relationship between molecular, radiologic, and clinical progression remains poorly characterized. A 66\u2010year\u2010old woman with\n KRAS<\/jats:italic>\n G12C<\/jats:sup>\n \/\n STK11<\/jats:italic>\n \/\n KEAP1<\/jats:italic>\n \u2010mutant lung adenocarcinoma received second\u2010line adagrasib after progression on chemo\u2010immunotherapy. Serial ctDNA monitoring by droplet digital PCR and targeted next\u2010generation sequencing was performed. Baseline\n KRAS<\/jats:italic>\n G12C<\/jats:sup>\n ctDNA (6205.3 copies\/mL) declined to 3.2 copies\/mL after 7\u2009weeks, indicating initial response. However, ctDNA levels rose to 21.1 copies\/mL at month 4 and 315.2 copies\/mL at month 6. Concurrent NGS revealed three emergent\n KRAS<\/jats:italic>\n mutations (G12D, G13D, Q61H), confirming polyclonal resistance. Notably, CT and MRI imaging remained stable by RECIST criteria throughout this period. Significant clinical deterioration, requiring prolonged hospitalization, occurred approximately 8\u2009weeks after initial ctDNA rise. The patient died 2\u2009months after detection of resistance mutations. In this case, NGS ctDNA detected three acquired\n KRAS<\/jats:italic>\n resistance mutations in addition to the original G12C, during a prolonged period of radiographic stability, illustrating polyclonal evolution under adagrasib pressure. These findings suggest that longitudinal liquid biopsy monitoring may provide early detection of resistance in\n KRAS<\/jats:italic>\n G12C<\/jats:sup>\n \u2010mutant NSCLC.\n <\/jats:p>","DOI":"10.1111\/1759-7714.70313","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:30:21Z","timestamp":1785389421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ctDNA<\/scp>\n Detection of Polyclonal\n \n KRAS<\/i>\n <\/scp>\n Resistance in Adagrasib\u2010Treated\n NSCLC<\/scp>"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0792-7103","authenticated-orcid":false,"given":"Marion","family":"Caumeil","sequence":"first","affiliation":[{"name":"Laboratoire de Biologie des Tumeurs Solides, CHU Montpellier Universit\u00e9 de Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Vendrell","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie des Tumeurs Solides, CHU Montpellier Universit\u00e9 de Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-7430","authenticated-orcid":false,"given":"Simon","family":"Cabello\u2010Aguilar","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie des Tumeurs Solides, CHU Montpellier Universit\u00e9 de Montpellier Montpellier France"},{"name":"MOBIDIC Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1904-2130","authenticated-orcid":false,"given":"Sarah","family":"Cavaillon","sequence":"additional","affiliation":[{"name":"Institut du Cancer de Montpellier (ICM) Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin Dominique","family":"Thomas","sequence":"additional","affiliation":[{"name":"Institut du Cancer de Montpellier (ICM) Montpellier France"},{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier (IRCM), Inserm Universit\u00e9 de Montpellier, Institut R\u00e9gional du Cancer de Montpellier (ICM) Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0293-6158","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Solassol","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie des Tumeurs Solides, CHU Montpellier Universit\u00e9 de Montpellier Montpellier France"},{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier (IRCM), Inserm Universit\u00e9 de Montpellier, Institut R\u00e9gional du Cancer de Montpellier (ICM) Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2103695"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204619"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105281"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04065-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.520"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00160","article-title":"Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors Through Longitudinal Analysis of Circulating Tumor DNA","volume":"2","author":"Dagogo\u2010Jack I.","year":"2018","journal-title":"JCO Precision 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