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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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).
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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Examples of improvements in humanised mouse models for PDX studies (PDF 155 kb)
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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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