Tumor evolution and drug response in patient-derived organoid models of bladder cancer

Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied and relatively lacking in suitable models. Here we describe a biobank of patient-derived organoid lines that recapitulates the spectrum of human bladder cancer at the histopathological and molecular levels. Organoid lines can be established efficiently from patient biopsies, including from patients before and after disease recurrence, and are interconvertible with orthotopic xenografts. Notably, these organoid lines often retain tumor heterogeneity and exhibit changes in their mutational profiles that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Overall, our studies indicate that patient-derived bladder tumor organoids represent a model system for studying tumor evolution and treatment response in the context of precision cancer medicine. We generated organoids from bladder tumor tissue. The organoids were trypsinized, plated in matrigel and overlaid with medium. The medium was changed every 3 days. After 14 days of plating, Organoids were harvested and processed for RNA isolation and transcriptome analysis using Ambion MagMAX RNA isolation kit.