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Nat Rev Cancer. 2017 Apr;17(4):254-268. doi: 10.1038/nrc.2016.140. Epub 2017 Jan 20.

Interrogating open issues in cancer precision medicine with patient-derived xenografts.

Author information

1
EurOPDX Consortium and are at the Royal College of Surgeons in Ireland, Dublin 2, Ireland.
2
EurOPDX Consortium and are at the Breast Cancer Now Research Unit, Division of Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Manchester M20 4QL, UK.
3
EurOPDX Consortium and are at the Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
4
The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
5
EurOPDX Consortium and are at the Vall d'Hebron Institute of Oncology, 08035 Barcelona, the Universitat Autònoma de Barcelona, 08193 Bellaterra, and the Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
6
CIBERONC, 08035 Barcelona, Spain.
7
EurOPDX Consortium and are at the Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
8
EurOPDX Consortium and are at Cancer Research UK Cambridge Institute, Cambridge Cancer Centre, University of Cambridge, Cambridge CB2 0RE, UK.
9
EurOPDX Consortium and is at the Institute of Biostatistics and Analyses, Faculty of Medicine, and Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masarykova Univerzita, 625 00 Brno, Czech Republic.
10
Hubrecht Institute, University Medical Centre Utrecht, and Princess Maxima Center for Pediatric Oncology, 3584CT Utrecht, The Netherlands.
11
EurOPDX Consortium and are at Lausanne Branch, Ludwig Institute for Cancer Research at the University of Lausanne, 1066 Lausanne, Switzerland.
12
EurOPDX Consortium and is at the Institut Curie, PSL Research University, Translational Research Department, 75005 Paris, and Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, 75006 Paris, France.
13
University of Colorado Cancer Center, Aurora, Colorado 80045, USA.
14
EurOPDX Consortium and is at the Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
15
EurOPDX Consortium and is at Beth Israel Deaconess Medical Center, Boston, Harvard Medical School, Boston, Massachusetts 02215, USA.
16
EurOPDX Consortium and is at the University Medical Centre Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
17
EurOPDX Consortium and are at The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
18
EurOPDX Consortium and are at the Department of Experimental Oncology, European Institiute of Oncology, 20139 Milan, Italy.
19
EurOPDX Consortium and are at Oslo University Hospital, Institute for Cancer Research, 0424 Oslo, Norway.
20
EurOPDX Consortium and are at Institut Curie, PSL Research University, Translational Research Department, 75005 Paris, France.
21
EurOPDX Consortium and is at the Laboratory for Molecular Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, and the Center for Cancer Biology, VIB, 3000 Leuven, Belgium.
22
EurOPDX Consortium and are at the Candiolo Cancer Institute IRCCS and Department of Oncology, University of Torino, 10060 Candiolo, Torino, Italy.
23
EurOPDX Consortium and are at the Vall d'Hebron Institute of Oncology and CIBERONC, 08035 Barcelona, Spain.
24
EurOPDX Consortium and is at the Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology ICO, Bellvitge Biomedical Research Institute IDIBELL, 08098 L'Hospitalet de Llobregat, Barcelona, and Xenopat S.L., Business Bioincubator, Bellvitge Health Science Campus, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
25
Seeding Science SAS, 75020 Paris, France.

Abstract

Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research.

PMID:
28104906
DOI:
10.1038/nrc.2016.140
[Indexed for MEDLINE]
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