Patient-Derived Urothelial Cancer Xenograft Models: A Systematic Review and Future Perspectives

Abstract

BACKGROUND: Lack of appropriate models that recapitulate the diversity, heterogeneity, and tumor microenvironment of urothelial cancer (UC) is a limitation to preclinical models. Patient-derived xenograft (PDX) models are a promising tool to overcome some of these issues, and thus we present an up-to-date and comprehensive overview of UC PDX models to aid in their future use. OBJECTIVE: To provide an overview on methodology, applications and limitations as well as future perspectives on bladder cancer PDX models. METHODS: Literature searches using PubMed and Web of Science databases were performed for relevant articles according to the following MeSH terms: "urothelial carcinoma(s)" OR "urothelial cancer" OR "urothelial tumor" OR "bladder cancer(s)" OR "bladder carcinoma(s)" OR "transitional cell carcinoma(s)" AND "xenograft(s)" OR "xenotransplant" at December 6th, 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 49 studies extracted, 41 studies after the year 2000 were finally analyzed. Published studies show that (1) UC PDX platforms retained the histology and genomic characteristics of the corresponding patient tumors. (2) UC PDX can be applied to ask various questions including to study the mechanisms of disease progression and treatment resistance, to develop novel drugs and biomarkers, as well as to potentially realize personalized drug selection. Recent topics of research using PDX have included the development of humanized mice as well as the use of 3D culture to complement some of the limitations of PDX models. CONCLUSIONS: UC PDX models serve as tools for understanding cancer biology, drug development and empowering precision medicine. The improvement of experimental systems using humanized mice to recapitulate the immune microenvironment of tumors will optimize UC PDX to study future questions in the field of immunotherapy.