Ovarian cancer patient-derived organoids and tumor xenografts as preclinical models for precision medicine

Abstract Background: Patient-derived organoids (PDO) and patient-derived xenografts (PDX) has been investigated as preclinical models for drug development and precision medicine. In this study, we established ovarian cancer PDOs and PDX models from Aug 2020 to Nov 2022, and developed protocols. Methods: We obtained tumor tissue from several sites (ovary, omentum, diaphragm, and peritoneum) or ascites from surgery of ovarian cancer patients. The tissue samples were dissociated for single cells and ascitic samples were centrifuged and washed to concentrate the tumor cells. Then, it is embedded in matrigel or basement membrane extract (BME) and seeded on a 24-well plate supplemented with culture medium containing modified growth factors. The association with clinical characteristics with success of model establishment were evaluated. Drug screening for organoids were designed on the 384-well plate using Celltiter-Glo 3D cell viability assay (Promega). The list of drugs consists of alkylating agent, monoclonal antibody, taxane, tyrosine kinase inhibitor (TKI), and poly(ADP-ribose) polymerase inhibitor (PARPi). For increase of success rate for xenograft, we compared intrabursa and subcutaneous injection xenograft models using ES-2 cell line then patient tumors in NOG mouse. Results: A total of 397 organoids passed first passage, however 32 (8%) organoids were continuously cultured over 5 passages. The associated clinical factors for establishment of organoids were stage (p=0.020, low stage 20% of success vs. high stage 2.4% of success) and pathologic types (p=0.035, low grade serous cancer (LGSC) 30% and clear cell 16.7% of success vs. high grade serous cancer (HGSC) 5.6% of success). Thirteen drugs were evaluated and AUC represented various range according to patient from 0.0004 to 1.3876. Three sites (ovary, omentum and ascites) established organoids from one patient represented difference in drug sensitivity which suggest role of cancer microenvironment. The growth upto 100mm3 of intrabursa injection (12.33 ± 0.6667) was faster than that of subcutaneous injection model (15.00 ± 1.000, p-value = 0.09) using ES-2 cell. Then comparison of patients tumor (N=10) into intrabursa vs. subcutaneous are undergoing with one completed case showing fast intrabursa growing. Conclusions: During relative short period we developed many PDOs and PDXs for future study including drug development. Moreover, we focused to develop better model for PDXs and it will give a new approach for successful model establishment. (This work was supported by National Research Foundation of Korea grant, founded by the Korea government (MSIT) [No.2020R1A2C2010566]) Citation Format: Yebeen Yu, Hye Ju Park, Cha Yeon Kang, Myong Cheol Lim, Sang Yoon Park, Yo Han Woo, Yun-Hee Kim, Sun-Young Kong. Ovarian cancer patient-derived organoids and tumor xenografts as preclinical models for precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 194.