Patient-derived xenografts as in vivo models for research in urological malignancies

Key Points Lack of appropriate models that recapitulate the complexity and heterogeneity of urological tumours precludes most of the preclinical reagents that enter clinical trials from achieving regulatory approval Patient-derived xenograft (PDX) models are characterized by direct engraftment of patient-derived tumour fragments into immunocompromised mice, improving preservation of the identity of the original tumours Use of urological tumour PDX models for analysing tumour biology and, more importantly, in drug development has increased Several agents targeting immune systems have shown promising results in kidney and bladder cancer, but they require PDX models established in mice with an intact immune system to trigger an immune response to the tumour International collaboration for sharing PDX models is a requisite for improving patient outcomes. Patient-derived xenograft (PDX) models can maintain the original histology and the molecular and genetic characteristics of the source tumour. Thus, PDX models have advantages over conventional models for drug development and treatment decisions in personalized medicine. In this Review, the authors discuss the potential of PDX models for both basic and clinical urological research. Lack of appropriate models that recapitulate the complexity and heterogeneity of urological tumours precludes most of the preclinical reagents that target urological tumours from receiving regulatory approval. Patient-derived xenograft (PDX) models are characterized by direct engraftment of patient-derived tumour fragments into immunocompromised mice. PDXs can maintain the original histology, as well as the molecular and genetic characteristics of the source tumour. Thus, PDX models have various advantages over conventional cell-line-derived xenograft (CDX) and other models, which has resulted in an increase in the use of urological tumour PDXs in the analysis of tumour biology and, importantly, for drug development and treatment decisions in personalized medicine. PDX models of urological malignancies have great potential to be used for both basic and clinical research, but limitations exist and need to be overcome. In particular, several agents targeting the immune system have shown promising results in kidney and bladder cancer; however, establishing PDX models in mice with an intact immune system so that an immune response against the tumour is triggered is important to investigate these new therapeutics. Moreover, international