Patient-Derived Bladder Cancer Organoid Models in Tumor Biology and Drug Testing: A Systematic Review

SIMPLE SUMMARY: Primary culture of cancer cells from patient tumors in a physiologically relevant system can provide information about tumor biology, disentangle the role of different cell types within the tumors, and give information about drug sensitivity for the development of cancer-targeted therapies and precision medicine. This requires the use of well-characterized and easily expandable tumor models. This review focuses on 3D models developed from primary human tissue including normal urothelium or bladder cancer samples, the characteristics of the models, and to what extent the organoids represent the diversity observed among human tumors. ABSTRACT: Bladder cancer is a common and highly heterogeneous malignancy with a relatively poor outcome. Patient-derived tumor organoid cultures have emerged as a preclinical model with improved biomimicity. However, the impact of the different methods being used in the composition and dynamics of the models remains unknown. This study aims to systematically review the literature regarding patient-derived organoid models for normal and cancer tissue of the bladder, and their current and potential future applications for tumor biology studies and drug testing. A PRISMA-compliant systematic review of the PubMED, Embase, Web of Sciences, and Scopus databases was performed. The results were analyzed based on the methodologies, comparison with primary tumors, functional analysis, and chemotherapy and immunotherapy testing. The literature search identified 536 articles, 24 of which met the inclusion criteria. Bladder cancer organoid models have been increasingly used for tumor biology studies and drug screening. Despite the heterogeneity between methods, organoids and primary tissues showed high genetic and phenotypic concordance. Organoid sensitivity to chemotherapy matched the response in patient-derived xenograft (PDX) models and predicted response based on clinical and mutation data. Advances in bioengineering technology, such as microfluidic devices, bioprinters, and imaging, are likely to further standardize and expand the use of organoids.