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

Nature Reviews Cancer volume 17, pages 254–268 (2017)Cite this article

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An Erratum to this article was published on 15 September 2017

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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.

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Figure 1: Strategies to generate humanized PDXs.
Figure 2: PDX preclinical study designs.

Change history

  • 15 September 2017

    In the online html version of this article, Joan Seoane's affiliations were not correct. He is also a member of the EurOPDX Consortium and is 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. This is correct in the print and PDF versions of the article.

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Acknowledgements

The authors would like to thank all members of the EurOPDX Consortium who also contributed to this article, and in particular S. Corso, S. Giordano, P. P. López-Casas, K. Moran-Jones and F. Nemati. The Caldas laboratory would like to thank the PGE team for their support, especially Lisa, Steve and Yi. A.T.B. is supported by Science Foundation Ireland under grants 13/CDA/2183 and 15/TIDA/2963 and further receives funding from the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT Grant CCRC13GAL. D.G.A. and R.B.C. are supported by Breast Cancer Now. F.A., E.H. and J.C.M. received KULeuven GOA funding (GOA/14/012) and a research grant from Stichting tegen Kanker. J.A. is funded by the Breast Cancer Research Foundation, the Spanish Association Against Cancer (AECC) and the Instituto de Salud Carlos III (PI16/00253 and CIBER-ONC). A.V.B. and D.K.C. are supported by Cancer Research UK (C29717/A17263), the Wellcome Trust (10372/Z/14/Z), the Scottish Genomes Partnership — SEHHD-CSO 1175759/2158447, the Howat Foundation and Pancreatic Cancer UK. A.B., C.C. and O.M.R. have been supported by funding from Cancer Research UK and by the European Union to the EUROCAN Network of Excellence (FP7; grant number 260791). E.B. is supported by the CETOCOEN PLUS project (CZ.02.1.01/0.0/0.0/15_003/0000469) and the RECETOX Research Infrastructure (LM2015051). G.C. and D.V. were funded by NIH transformative R01CA156695 and European Research Council (ERC) Advanced grant 1400206AdG-322875. S.G.E. receives support from NCI grant 1UM1CA186688 for early-phase trials through the ET-CTN. E.G.S. is supported by the Spanish Ministry of Economy and Competitivity MINECO and from the ISCIII (SAF2014-55997; PIE13/00022, co-funded by FEDER funds/ European Regional Development Fund (ERDF) — a way to build Europe), by a Career Catalyst Grant from the Susan Komen Foundation (CCR13262449) and by a European Research Council Consolidator grant (CoG682935). M.A.J. is supported by an Irish Health Research Board Health Research Award (#HRA-POR-2014-547). S.D.J. is supported by the Dutch Cancer Society (grants RUG 2010-4833, RUG 2011-5231, RUG 2012-5477 and RUG 2014-6691). J.J. is funded by the Dutch Cancer Society (NKI 2011-5197 and EMCR 2014-7048), the Netherlands Organisation for Scientific Research (Zenith 93512009, Vici 91814643, CancerGenomiCs.nl) and the European Research Council (ERC-SyG CombatCancer). K.K. and D.S.P. are supported by the Dutch Cancer Society (NKI-2013-5799). L.L. and P.G.P. are funded by ERC Advanced Grant 341131 and Italian Association for Cancer Research (AIRC) Investigator Investigator Grant 14216. G.M.M. receives funds from the Norwegian Cancer Society (421851) and the Research Council of Norway (222262/F20). J.H.N. is funded by the Research Council of Norway under grant 250459/F20. H.G.P. is supported by the Instituto de Salud Carlos III and the Miguel Servet Program (MSII14/00037). V.S. is supported by the Instituto de Salud Carlos III (PI13/01714 and the Miguel Servet Program CP14/00028), by a Career Catalyst Grant from the Susan Komen Foundation CCR15330331 and the FERO Foundation. L.S. was funded by Worldwide Cancer Research (WCR/AICR Grant #13-1182), the European Research Council (CoG Grant #617473), the Instituto de Salud Carlos III (FIS Grant #PI13/01705) and the FERO Foundation. A.V. is supported by the Instituto de Salud Carlos III (PI13/0133 and PIE13/00022 (Oncoprofile)), Fundación Mutua Madrileña AP150932014 and a grant from the Spanish Association Against Cancer from Barcelona, AECC. A.B. is supported by AIRC (Investigator Grant project 15571). L.T. and E.M. are supported by the AIRC (Special Programme Molecular Clinical Oncology 5 × 1000, project 9970, and Investigator Grant projects, 14205 to L.T. and 12944 to E.M.) and also receive funding from the Fondazione Piemontese per la Ricerca sul Cancro-ONLUS (5 × 1000 Italian Ministry of Health 2011).

Author information

Authors and Affiliations

  1. EurOPDX Consortium and are at the Royal College of Surgeons in Ireland, 2, Dublin, Ireland

    Annette T. Byrne & Monika A. Jarzabek

  2. Division of Molecular and Clinical Cancer Sciences, EurOPDX Consortium and are at the Breast Cancer Now Research Unit, Manchester Cancer Research Centre, University of Manchester, Manchester, M20 4QL, UK

    Denis G. Alférez & Robert B. Clarke

  3. EurOPDX Consortium and are at the Katholieke Universiteit Leuven, 3000, Leuven, Belgium

    Frédéric Amant, Daniela Annibali & Els Hermans

  4. The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands

    Frédéric Amant

  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.,

    Joaquín Arribas, Joan Seoane & Laura Soucek

  6. CIBERONC, Barcelona, 08035, Spain

    Joaquín Arribas & Joan Seoane

  7. EurOPDX Consortium and are at the Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK

    Andrew V. Biankin & David K. Chang

  8. EurOPDX Consortium and are at Cancer Research UK Cambridge Institute, Cambridge Cancer Centre, University of Cambridge, Cambridge, CB2 0RE, UK

    Alejandra Bruna, Carlos Caldas & Oscar M. Rueda

  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, Brno, 625 00, Czech Republic

    Eva Budinská

  10. Hubrecht Institute, University Medical Centre Utrecht, and Princess Maxima Center for Pediatric Oncology, Utrecht, 3584CT, The Netherlands

    Hans Clevers

  11. EurOPDX Consortium and are at Lausanne Branch, Ludwig Institute for Cancer Research at the University of Lausanne, Lausanne, 1066, Switzerland

    George Coukos & Dominique Vanhecke

  12. Translational Research Department, EurOPDX Consortium and is at the Institut Curie, PSL Research University, 75005, Paris

    Virginie Dangles-Marie

  13. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, Paris, 75006, France

    Virginie Dangles-Marie

  14. University of Colorado Cancer Center, Aurora, 80045, Colorado, USA

    S. Gail Eckhardt

  15. EurOPDX Consortium and is at the Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute IDIBELL, L'Hospitalet de Llobregat, Barcelona, 08908, Spain

    Eva Gonzalez-Suarez

  16. EurOPDX Consortium and is at Beth Israel Deaconess Medical Center, Boston, Harvard Medical School, Boston, 02215, Massachusetts, USA

    Manuel Hidalgo

  17. EurOPDX Consortium and is at the University Medical Centre Groningen, University of Groningen, Groningen, 9713GZ, The Netherlands

    Steven de Jong

  18. EurOPDX Consortium and are at The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands

    Jos Jonkers, Kristel Kemper & Daniel S. Peeper

  19. EurOPDX Consortium and are at the Department of Experimental Oncology, European Institiute of Oncology, Milan, 20139, Italy

    Luisa Lanfrancone & Pier Giuseppe Pelicci

  20. EurOPDX Consortium and are at Oslo University Hospital, Institute for Cancer Research, 0424, Oslo, Norway

    Gunhild Mari Mælandsmo & Jens Henrik Norum

  21. Translational Research Department, EurOPDX Consortium and are at Institut Curie, PSL Research University, Paris, 75005, France

    Elisabetta Marangoni & Sergio Roman-Roman

  22. Department of Oncology, EurOPDX Consortium and is at the Laboratory for Molecular Cancer Biology, Katholieke Universiteit Leuven, and the Center for Cancer Biology, VIB, 3000 Leuven, Belgium.,

    Jean-Christophe Marine

  23. EurOPDX Consortium and are at the Candiolo Cancer Institute IRCCS and Department of Oncology, University of Torino, Candiolo, 10060, Torino, Italy

    Enzo Medico, Andrea Bertotti & Livio Trusolino

  24. EurOPDX Consortium and are at the Vall d'Hebron Institute of Oncology and CIBERONC, Barcelona, 08035, Spain

    Héctor G. Palmer, Alejandro Piris-Gimenez & Violeta Serra

  25. 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

    Alberto Villanueva

  26. Xenopat S.L., Business Bioincubator, Bellvitge Health Science Campus, 08907 L'Hospitalet de Llobregat, Barcelona, Spain

    Alberto Villanueva

  27. Seeding Science SAS, Paris, 75020, France

    Emilie Vinolo

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Corresponding authors

Correspondence to Annette T. Byrne or Livio Trusolino.

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Competing interests

Grants from Celgene and Boehringer-Ingelheim, honoraria from Roche and Genentech, consultancy for Roche, Genentech, Novartis and Sanofi-Aventis (G.C.), consultancy for Oncodesign and funding by Novartis (S.R.R.), founder of the spin-off Xenopat S.L. (A.V.). The other authors declare no competing interests.

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Byrne, A., Alférez, D., Amant, F. et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer 17, 254–268 (2017). https://doi.org/10.1038/nrc.2016.140

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