Developing patient-derived organoid and xenograft models for preclinical assessment in ovarian cancer

Background: Ovarian cancer (OC) is a highly lethal malignancy, characterized by late-stage diagnosis, marked tumor heterogeneity, and poor overall prognosis. Preclinical models of OCs, including patient-derived organoids (PDO) and xenografts (PDX), has been investigated for drug development and precision medicine. In this study, we established OC PDOs and PDX models Methods: Tumor tissue were collected from multiple sites (ovary, omentum, diaphragm, and peritoneum) or ascites during surgery. After tissue dissociation, single cells were embedded in basement membrane extract for PDO culture and injected either intrabursally or subcutaneously into immunodeficient mice (NOD/Shi-scid IL-2Rν null ) to generate PDXs. PDOs were successfully cultured beyond five passage, and drug screening across 14 drugs including platinum-based agents, taxanes, topoisomerase inhibitors, and PARP inhibitors was performed using the CellTiter-Glo 3D viability assay. PDXs tumor growth were monitored three times a week, and analyzed the time points to reach 100 mm 3 . Results: A total of 18 PDOs were successfully established from 14 advanced-stage OC patients with diverse histological and genetical characteristics. Drug screening demonstrated a variable range of responses with the area under the curve ranging from 0.29 to 1.00, especially to platinum-based drugs and PARP inhibitors. The OC PDX model was successfully established in 9 (26.5%) out of 34 patients. Overall, the duration until 100 mm 3 tumor growth was shorter in intrabursal models compared to subcutaneous models with mean times of 90.3 days (n = 4) and 149.8 days (n = 9), respectively. Notably, tumor formation accelerated with successive passages, suggesting enhanced engraftment efficiency and growth kinetics in later generations. Conclusions: We successfully developed OC PDO and PDX models that preserve tumor heterogeneity. These models enable detailed investigation of tumor biology offering critical insights for the development of novel treatment strategies. This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT): RS-2025-19542979, RS-2025-25437292