Abstract 3417: Development of a patient-derived pancreatic cancer organoid-CAF coculture model to study tumor microenvironment influence on radiotherapy response

Abstract Introduction: Radiotherapy (RT) is a fundamental treatment modality for pancreatic ductal adenocarcinoma (PDAC) at all disease stages. However, local relapse, driven by treatment resistance, remains a critical issue for improving patient outcomes. While tumor cell-intrinsic factors contribute to resistance, evidence indicates that the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), plays a crucial role through different mechanisms. Current patient-derived organoid (PDO) models fail to authentically recapitulate CAF-tumor interactions and their influence on RT response, limiting their translational relevance. We developed a coculture system to better mimic these interactions and enable physiologically relevant radiobiological studies. Methods: PDOs of PDAC and primary CAFs were cocultured in 3D suspension in ultra-low attachment plates with 300ug/mL of Matrigel. The structural integrity and composition of the resulting aggregates were characterized using H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3417.