Abstract A032: Quantification of tumor heterogeneity and functional drug response from patient-derived organoids highly correlates with progression-free survival of pancreatic cancer patients in a clinical trial
Authors: Abraham Lin, Maxim Le Compte, Edgar Cardenes De La Hoz, Tyler Gilcrest, Geert Roeyen, Filip Lardon, Christophe Deben
Journal: Cancer Research (2025)

Abstract Patient-derived tumor organoids (PDOs) preserve the clonal heterogeneity, mutational landscape, and histological architecture of the originating patient tumor, positioning them as promising laboratory surrogates for predicting clinical therapy response1-2. However, current PDO assays, such as CellTiter-Glo3D, fail to accurately reflect drug responses by quantifying proxy parameters like intracellular ATP3,4. Newer assays include live-imaging, where PDOs are screened with therapeutic compounds and imaged over time to visualize their drug response. Despite generating enormous amounts of image data, current analysis tools are labor- and resource-intensive and produce simple readouts originally designed for 2D cell monolayers (e.g. counts, size, relative viability). These limitations have greatly hindered the predictive capability of PDOs5,6. Therefore, there is significant unmet need to develop highly dimensional computational tools to unlock the predictive potential of organoids for more personalized medicine. In this study, we dynamically quantified PDO drug response on the single-organoid resolution from live-images, to unravel patient-specific tumor heterogeneity and responses to therapies7. A fully characterized organoid panel from pancreatic ductal adenocarcinoma(PDAC) patients (n=8) was used, and we matched our PDO analysis with retrospective clinical patient response to standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX). Our results demonstrated that our PDO analysis method identified patient-specific sensitives to therapy that were in-line with clinical outcomes, and our readouts highly correlated with progression-free survival of matched patients (R=0.97). This represents a significant improvement over current drug response readouts – relative viability (R=0.20). This work highlights the need for functional PDOs analysis to capture the biological complexities and improve clinical translatability in the emerging era of personalized medicine. References: 1. Seppala, T.T., et al. Ann Surg 272 (2020) 2. Hadj Bachir, E., et al. Biol Cell 114 (2021) 3. Sachs, N., et al. Cell 172 (2018) 4. Kijima, T., et al. Cell Mol Gastroenterol Hepatol 7 (2019) 5. Ooft, S.N., et al. Sci Transl Med 11(2019). 6. Driehuis, E., et al. Proc Natl Acad Sci 116 (2019) 7. Le Compte, M., et al. npj Precis Oncol (2023). Citation Format: Abraham Lin, Maxim Le Compte, Edgar Cardenes De La Hoz, Tyler Gilcrest, Geert Roeyen, Filip Lardon, Christophe Deben. Quantification of tumor heterogeneity and functional drug response from patient-derived organoids highly correlates with progression-free survival of pancreatic cancer patients in a clinical trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A032.