Abstract 5186: Organoids from patient-derived xenograft (PDXO) for preclinical therapeutic predictions

Tumors exhibit heterogeneity, comprising diverse cell clones, necessitating the use of preclinical models that accurately replicate clinical properties for cancer research and antitumor efficacy prediction. Patient-derived xenograft (PDX) models recapitulate key characteristics of human tumors, but are cost-intensive and time-consuming, thus unsuitable for large-scale screenings. Here, we evaluated the biological equivalence of organoid models derived from patient-derived xenograft tumors (PDXO) to PDXs. PDX organoids (PDXO) are small, organized three-dimensional structures developed from PDX tissue fragments in specialized in vitro culturing systems, enabling early-stage assessment of drugs. We have demonstrated that PDXOs are similar to their corresponding PDX counterparts in multiple aspects. Pathological staining (HE & IHC) data confirmed the heterogeneity of tissue architecture, cellular composition, and microenvironment interactions inherited from PDX. Genomic analysis showed the preservation of molecular and biological characteristics. In vitro pharmacological studies demonstrated that the sensitivity of PDXOs to drugs was similar to that of the original PDX models. Furthermore, in some cases where pairs of PDXs were established from the same patient before and after targeted treatment, the corresponding PDXOs reproduced the sensitivity differences observed during in vivo studies, as well as similar mechanisms of resistance development. These clinically analogous results highlight the potential of PDXOs for preclinical and clinical drug testing, enabling more precise predictions of therapeutic outcomes. Citation Format: Chao Zhang, Xiaoying Zhuang, Lu Yin, Xiaoyi Xing, Sen Wang, Zizhuo Chen, Lei Jin, Qiangqiang Fan, Jiaping Sun, Fuyang Wang, Wenjie Gao, Qingyang Gu. Organoids from patient-derived xenograft (PDXO) for preclinical therapeutic predictions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5186.