Abstract 42: Non-small cell lung cancer (NSCLC) patient derived xenograft organoids (PDX-O) as a model for testing novel therapeutic approaches

Abstract Despite advances in therapy and early screening, non-small cell lung cancer (NSCLC) remains responsible for the most cancer-related deaths worldwide. There is an urgent need to elucidate the drivers of NSCLC progression to develop better treatment options, but these efforts are often limited by a lack of clinically relevant model systems. To address this need, we developed a series of patient-derived xenografts (PDX) from a clinical study of tumor metabolism. We confirmed that these models retain the genetic, metabolic, and metastatic phenotypes of the patient tumor. Furthermore, we developed patient-derived organoids (PDOs) from these systems by growing and passaging PDX cells in Matrigel droplets with the ThermoFisher OncoPro System. Preliminary validation studies have revealed these organoids have expected morphology, high viability, and maintenance of NSCLC expression markers. We have used these novel model systems to identify heterogeneous metabolic phenotypes and identify targetable vulnerabilities. Specifically, we have used a drug screening approach to combine metabolic inhibitors with standard of care chemotherapies to evaluate combinatorial treatment strategies in NSCLC by cancer cell death. In summary, we have developed a bedside-to-bench approach of identifying patient-relevant tumor biology, in tractable, testable systems, and we use these models to identify novel therapeutic approaches in NSCLC. Citation Format: Maia G. Clare, Robert B. Cameron, Nia G. Hammond, Massar Alsamraae, Brandon Faubert. Non-small cell lung cancer (NSCLC) patient derived xenograft organoids (PDX-O) as a model for testing novel therapeutic approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 42.