Functional characterization and therapeutic response differences between orthotopic and subcutaneous patient-derived xenograft models

Abstract Subcutaneous patient-derived xenografts (PDXs) have provided the research community with translational models to interrogate cancer biology and assist in drug development. Orthotopic PDXs provide an even more clinically relevant model system that recapitulates the tumor environment aspects of the human disease. Here, we compare the differences in gene expression signatures of PDX models when implanted subcutaneously or orthotopically. Furthermore, we evaluate differences in in-vivo pharmacological response between the two model systems and identify several functional characterizations that selectively enhance pharmacological response in favor of the orthotopic model. Citation Format: Jonathan Nakashima, Long Do, Warren Andrews, Yuan-Hung Chien, Christophe Pedros, Jantzen Sperry, Bianca Carapia, Deborah Yan, Giovanni Rivera, Arun Singh, Fritz C. Eilber, Brian Datnow. Functional characterization and therapeutic response differences between orthotopic and subcutaneous patient-derived xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3118.