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

Nature Reviews Urology volume 14, pages 267–283 (2017)Cite this article

Subjects

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.

Abstract

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 collaboration to share PDX models is essential for research concerning fatal urological tumours.

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Figure 1: Subcutaneous transplantation of patient-derived xenografts.
Figure 2: Application of patient-derived xenograft models in urological cancer.

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Authors and Affiliations

  1. Department of Urology, Kyoto University Graduate School of Medicine, 54 Kawaharacho Shogoin Sakyo-ku, Kyoto, 6068507, Japan

    Takahiro Inoue, Naoki Terada, Takashi Kobayashi & Osamu Ogawa

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  1. Takahiro Inoue
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  2. Naoki Terada
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T.I., N.T., T.K., and O.O. researched the data for the article. All authors substantially contributed to discussion of content, wrote the manuscript, and reviewed and edited the manuscript before submission.

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Correspondence to Osamu Ogawa.

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Prostate cancer patient-derived xenograft (PDX) models. (DOC 102 kb)

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Urothelial cancer patient-derived xenograft PDX models. (DOC 148 kb)

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Inoue, T., Terada, N., Kobayashi, T. et al. Patient-derived xenografts as in vivo models for research in urological malignancies. Nat Rev Urol 14, 267–283 (2017). https://doi.org/10.1038/nrurol.2017.19

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