Abstract 2170: Patient-derived orthotopic xenograft models predict chemotherapeutic response in pancreatic ductal adenocarcinoma: an emerging platform for translational research.

Abstract Background: Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer death. Current chemotherapy options are centered on a gemcitabine as backbone. However, the chemotherapy responsive rate and prognosis are still very poor with a five-year survival rate of 13%. Animal models mimicking tumor microenvironment have been used for pre-clinical and therapeutic studies, but the subcutaneous xenograft model does not replicate the clinical location and human PDAC chemotherapy responses. In this study, we used patient-derived orthotopic xenograft (PDOX) mouse models, with tumors localized to the pancreases, that mimic the natural tumor microenvironment, to test the efficacy of chemotherapeutic gemcitabine on PDAC progression and compare to their clinical response. Methods: Totally 71 PDAC patients were consented and their tumor/blood specimens were collected after reviewed by pathologists. Tumor cells from one representative partial/moderate chemo-responding PDAC patients (PaCa23) and one representative poor chemo-responding PDAC patient (PaCa54), were expanded, isolated and intra-pancreas injected to NOD/SCID mice. Gemcitabine (100 mg/kg) was administered weekly by intravenous infusion for 4 weeks. Tumor volumes and mouse body weights were monitored weekly. After mice were euthanized, tumors were collected for tumor weight measurement. Hematoxylin 0.05). Conclusion: Our PDOX mouse model successfully recapitulates key histopathological and microenvironmental features of human PDAC and reflects patient-specific responses to gemcitabine treatment. The differential tumor response observed in PaCa23 and PaCa54 models mirrors their respective clinical outcomes, underscoring the predictive value of this platform. This orthotopic model holds significant promise as a preclinical tool for evaluating chemotherapeutic efficacy, guiding personalized therapy strategies, and studying tumor biology within a clinically relevant microenvironment. Citation Format: Xin Zhang, Nathan Bolton, Alicia Ray, Grace Maresh, Rachel Graham, Li Li. Patient-derived orthotopic xenograft models predict chemotherapeutic response in pancreatic ductal adenocarcinoma: an emerging platform for translational research abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2170.