A bladder cancer patient-derived xenograft reflects aggressive growth dynamics in vivo and in organoids

A MIBC patient with aggressive disease course was selected for ex vivo model establishment and growth dynamic studies. After standard neoadjuvant treatment with gemcitabine and cisplatin, cystectomy was performed, and excised urothelial carcinoma tissue was implanted subcutaneously into male SCID mice to generate CoCaB1 PDXs. Established PDXs were passaged subcutaneously in SCID mice to generate early and late passage models for functional and molecular characterization. Representative early and late passage PDXs were collected for organoid establishment. Bladder cancer is among the most prevalent cancers worldwide, but few well-characterized and representative laboratory models exist for use in therapy development. Here, we establish and molecularly characterize CoCaB1, a muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. PDX and organoids demonstrate concordant acceleration in growth upon serial passaging, suggesting the expansion of aggressive subclones. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition. Despite transcriptional changes, our models successfully maintained the histological identity and mutational heterogeneity of their parental tumor. These studies establish the CoCaB1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies.