Large animal models are being used more often for studying diseases including gastrointestinal (GI) disorders. The dog model shares similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To expand the translational potential of the dog model, we developed a three-dimensional (3D) canine GI organoid system, which provides translational advantages over commonly used models, such as the rodent (1). Increases in our understanding of key signaling pathways within the intestinal stem cell niche growth and maintenance, has allowed for the development of fully differentiated epithelial cells in 3D organoids. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures (1). These organoids are relevant in studying the absorption of oral medications for subjects who suffer from GI disorders. The purpose of this study was to investigate the biologic activity of the NSAID piroxicam, and chemotherapeutic agents Doxorubicin and Mitomycin C, using our organoid system, for the treatment of transitional cell carcinoma (TCC). Effective therapies for TCC are limited, with objective response rates to most chemotherapeutic regimens below 20% (2). Ongoing translational research on organoids derived from dogs with naturally occurring digestive disorders has the potential to improve the predictability of preclinical models used for optimizing the therapeutic management of severe chronic enteropathies in human patients.