{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:35:49Z","timestamp":1784892949220,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"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>Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and a leading cause of cancer-related death. Despite therapeutic advances, long-term survival in stage IV disease is uncommon. Tumor analyses that combine genomic and functional platforms may provide the opportunity to monitor clonal dynamics and guide therapy selection. Case Presentation: We report a 67-year-old woman with metastatic poorly differentiated lung adenocarcinoma, who achieved four durable remissions and survived nearly 12 years. Serial studies using ex vivo analysis of programmed cell death (EVA\/PCD) functional-profiling-guided therapeutic choices were correlated with next-generation sequencing (NGS). Molecular events included the emergence of a BRAF V600E mutation responsive to dabrafenib plus trametinib and the acquisition of an EGFR exon 19 deletion responsive to Osimertinib. EVA\/PCD identified activity for targeted agents and revealed synergy for vinorelbine plus Osimertinib not predicted by genomic profiling, which provided additional response. Discussion: This case highlights clonal evolution in NSCLC and illustrates how serial tissue analyses correlating phenotypic and genomic events can offer therapeutic interventions to provide long-term survival. Conclusions: The integration of functional and genomic profiling may improve personalized treatment in NSCLC by interrogating tumor heterogeneity and clonal evolution to inform rational therapeutic selection.<\/jats:p>","DOI":"10.3390\/curroncol32110646","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:17:27Z","timestamp":1763551047000},"page":"646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Serial Functional and Genomic Analyses Illuminate Clonal Evolution in Metastatic NSCLC with 12-Year Survival"],"prefix":"10.3390","volume":"32","author":[{"given":"Vikrant S.","family":"Bakaya","sequence":"first","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick C.","family":"Phu","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas A.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S.","family":"Evans","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"},{"name":"Metabolomycs, Inc., 750 E. 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula J.","family":"Bernard","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico R.","family":"Francisco","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"Nagourney","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Torres","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John","family":"Henry","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"},{"name":"Metabolomycs, Inc., 750 E. 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-5340","authenticated-orcid":false,"given":"Paulo","family":"D\u2019Amora","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"},{"name":"Metabolomycs, Inc., 750 E. 29th Street, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Nagourney","sequence":"additional","affiliation":[{"name":"Nagourney Cancer Institute, 750 East 29th Street, Long Beach, CA 90806, USA"},{"name":"Metabolomycs, Inc., 750 E. 29th Street, Long Beach, CA 90806, USA"},{"name":"Department of Obstetrics and Gynecology, University of California Irvine (UC Irvine), 101 The City Dr S, Orange, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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