Towards Best Practice in Establishing Patient-Derived Xenografts

Chapter
Part of the Molecular and Translational Medicine book series (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.

Keywords

Patient-derived xenograft Tumour graft Metastasis Subcutaneous Renal capsule Orthotopic Immunocompromised mice Prostate cancer Breast cancer 

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

Notes

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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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Prostate Research Group, Cancer Program - Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer ConsortiumMonash UniversityClaytonAustralia
  2. 2.Prostate Cancer Translational Research Program, Cancer Research DivisionPeter MacCallum Cancer CentreMelbourneAustralia
  3. 3.Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneAustralia
  4. 4.Prostate Research Group, Cancer Program - Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer ConsortiumMonash UniversityClaytonAustralia

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