Abstract IA17: Patient-derived organoid models of bladder cancer

Abstract The molecular mechanisms of bladder tumorigenesis are poorly understood, in part due to the lack of suitable model systems that reflect the biology of human bladder cancer. In our studies, we have used three-dimensional culture approaches to establish a novel biobank of human patient-derived organoids from primary bladder tumors. These organoid lines recapitulate the histopathologic and molecular diversity of non-muscle invasive bladder cancer as well as muscle-invasive bladder cancer, and can be readily converted into xenografts by orthotopic transplantation. These organoid lines can be propagated by serial passaging in culture while maintaining their tumor properties and display mutational profiles that are highly concordant with their parental tumors. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Furthermore, we have shown that these organoid lines are highly amenable for analyses of drug response, which can be validated in vivo using orthotopic xenografts. I will discuss our recent findings using patient-derived tumor organoid lines to investigate bladder cancer biology and drug response, including ongoing analyses of tumor plasticity and the basis for tumor recurrence. Citation Format: Michael M. Shen. Patient-derived organoid models of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA17.