Abstract
The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific clinical responses. PDX models are an important platform to address the contribution of inter-tumoral heterogeneity to therapeutic sensitivity, tumor evolution, and the mechanisms of treatment resistance. With the increasingly important role played by targeted therapies in urological malignancies, the establishment of representative PDX models can contribute to improved facilitation and adoption of precision medicine. In this review of the evolving role of the PDX in urothelial cancer and kidney cancer, we discuss the essential elements of successful graft development, effective translational application, and future directions for clinical models.
Highlights
The increasingly recognized complexity of human cancers and the heterogeneity of malignant tumor cells have posed a major challenge to development of effective therapies in urologic oncology
Molecular subtyping of both bladder cancer and renal cell carcinoma (RCC) is an area of clinical research with important implications for patient-derived xenograft (PDX) models
It is important for any researcher working with patient-derived xenografts or patient-derived cell lines to be aware of the potentially confounding effect that xenotropic murine retroviruses (XMRV) can have on growth parameters
Summary
The increasingly recognized complexity of human cancers and the heterogeneity of malignant tumor cells have posed a major challenge to development of effective therapies in urologic oncology. The first reports of utilization of this technique on urologic malignancies, namely urothelial carcinoma and renal cell carcinoma (RCC), were published in the 19700 s [5,6,7] Since this time, PDX models have increased in their prevalence, serving to improve our understanding of both bladder and kidney cancers. While the oncology community remains optimistic that PDX models will one day serve as “mouse avatars,” providing patients and their clinicians with real-time information on tumor therapy response and tumor evolution, PDX models are not yet capable of serving as a decision-making tool Their role in the study of kidney and bladder cancers continues to expand, improving our understanding of disease biology. PDX models have the potential to define treatment modality and sequencing in both the localized and advanced settings for kidney and bladder cancers
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