Establishing 3D Organoid Models from Patient-Derived Conditionally Reprogrammed Cells to Bridge Preclinical and Clinical Insights in Pancreatic Cancer

Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options. To address the limitations of traditional 2D cell culture models, we developed 3D organoid cultures from patient-derived conditionally reprogrammed cell (CRC) lines. These organoids retain the molecular and mutational profiles of the original tumor cells, providing a more accurate model for drug response prediction. Drug sensitivity assays using gemcitabine plus nab-paclitaxel (Abraxane) and FOLFIRINOX revealed that 3D organoids more closely reflect clinical outcomes than 2D cultures, with higher IC50 values consistent with in vivo drug resistance. This platform offers a promising approach for precision medicine in pancreatic cancer. Organoids were established to compare the genetic and molecular characteristics of cells cultured under 2D and 3D conditions, using RNA-seq for transcriptomic profiling.