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Towards Best Practice in Establishing Patient-Derived Xenografts

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Patient-Derived Xenograft Models of Human Cancer

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

It is remarkable that human tumour tissues can be grown for months, or even years, as serially transplantable, patient-derived xenografts (PDXs) in immunocompromised mice. The grafting technique used has been refined over the last few decades, so it is now possible to successfully engraft most tumour types, albeit with varying take rates. This review focuses on the methodological requirements to establish successful PDXs. The first step is selecting viable tumour tissue from surgical resections of local or metastatic disease, ascites, pleural effusions, biopsies, circulating tumour cells, rapid autopsies or even organoids. Once grafts are prepared, sometimes with Matrigel or stroma, their likelihood of growing is affected by the strain of immunocompromised host mice and the graft site, which may be subcutaneous, subrenal capsule or orthotopic. Finally, once PDXs are established, authentication assays can be used to rule out possible misidentification or cross-contamination following serial passaging. By carefully optimising all of these steps, PDXs can be grown as efficiently as possible, providing invaluable models for preclinical cancer research.

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Abbreviations

NOD-SCID:

Non-obese diabetic severe combined immunodeficient mice

CTC:

Circulating tumour cell

NK cell:

Natural killer cell

NSG:

NOD-SCID interleukin-2 receptor gamma chain null mice

PAS:

PDX Authentication System

PDX:

Patient-derived xenograft

SCID:

Severe combined immunodeficient mice

SNP:

Single nucleotide polymorphism

STR:

Short tandem repeat

TURP:

Transurethral resection of the prostate

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Acknowledgements

We thank Laura Porter for her help preparing the manuscript. The Monash University Prostate Cancer Research Program is supported by funding from the Peter and Lyndy White Foundation, the EJ Whitten Foundation and TissuPath Pathology. GPR is supported by a fellowship from the National Health and Medical Research Council (1102752).

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Authors and Affiliations

  1. Prostate Research Group, Cancer Program - Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, 3000, Australia

    Gail P. Risbridger

  2. Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3800, Australia

    Gail P. Risbridger

  3. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, 3010, Australia

    Gail P. Risbridger

  4. Prostate Research Group, Cancer Program - Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, VIC, 3800, Australia

    Mitchell G. Lawrence

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  1. Gail P. Risbridger
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Correspondence to Mitchell G. Lawrence .

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  1. Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Yuzhuo Wang

  2. Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, British Columbia, Canada

    Dong Lin

  3. Living Tumor Laboratory, BC Cancer Agency/Vancouver Prostate Centre, Vancouver, British Columbia, Canada

    Peter W. Gout

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Risbridger, G.P., Lawrence, M.G. (2017). Towards Best Practice in Establishing Patient-Derived Xenografts. In: Wang, Y., Lin, D., Gout, P. (eds) Patient-Derived Xenograft Models of Human Cancer . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55825-7_2

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