Abstract 1667: Comparison of drug responses using patient-derived xenograft (PDX) and patient-derived organoid (PDO) models from treatment-refractory breast cancer

Abstract

Abstract Background: Patient-derived xenografts (PDX) and organoids (PDO) have become important translational model systems for cancer research, especially for drug responses prediction. Since PDX models have limitation as low success rate and takes long time, PDO is emerging as a new technique. Here, we compared the drug responses in PDX and PDO models using tissues obtained from treatment-refractory breast cancer patients. Methods: Tumor tissues from breast cancer patients were implanted into the mammary fat pads of immunodeficient mice. Tumor size of mice were measured 3 times a week using digital caliper. When xenograft tumors reached 200mm3 in size, drug treatment was started. Drugs selection was based on gene expression patterns, the presence of available drugs, and clinical treatment history. The organoids were established from PDX tumor pieces. Organoids were seeded and cultured in 96-well plates (2000 cells per well) for drugs testing. We treated with a single or combination drugs in PDX and PDO models. For interpretation of drug sensitivity results of PDO or PDX, we referred to IC50 database of 2D cell lines or results from references. Results: We compared the drugs response efficacy in five cases with paired PDX and PDO models; 1 hormone receptor (HR) positive+; HER2 negative-, 1 HR+;HER2+ and 3 TNBC (triple-negative breast cancer) subtypes. In HR+;HER2- case, drug test results between PDX and PDO partially matched in single treated group. In HR+;HER2+, the results of combination treated groups were partially matched in PDX and PDO model. The results for two TNBC samples matched in single or combination treated groups. Especially, tumor size or cell viability of one TNBC case showed significant differences between control and sorafenib/everolimus combination treated groups. The other case of TNBC type had partially matched in PDX and PDO model. We will analyze the consistency for the genomic profiles of tumors in patients, PDX, and PDO models. Conclusion: We have compared the various drugs responses through the successful establishment of PDO and PDX from the different breast cancer subtypes. Although the results are not perfectly matched, it showed that these models have potential to assist the chemotherapy strategies for each patient and predict outcome of treated patient's prognosis. In the future, we will be focused on explaining why the results of drug response between PDX and PDO were inconsistent. (This study was supported by National Cancer Center, Korea, 1710450, and 1810101) Citation Format: Jin-Sun Ryu, You-sun Noh, Bo-Ra Kim, Yun-Hee Kim, A-Ra Jeon, Sung Hoon Sim, In Hae Park, Eun Gyeong Lee, Eun Sook Lee, Keun Seok Lee, Sun-Young Kong. Comparison of drug responses using patient-derived xenograft (PDX) and patient-derived organoid (PDO) models from treatment-refractory breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1667.