title: Interrogating open issues in cancer precision medicine with patient-derived xenografts.
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.
authors.affiliation: EurOPDX Consortium and are at the Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Annette T
authors.initials: AT
authors.lastname: Byrne
authors.affiliation: 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.
authors.forename: Denis G
authors.initials: DG
authors.lastname: Alférez
authors.affiliation: EurOPDX Consortium and are at the Katholieke Universiteit Leuven, 3000 Leuven, Belgium.|The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
authors.affiliation: EurOPDX Consortium and are at the Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Daniela
authors.initials: D
authors.lastname: Annibali
authors.affiliation: 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.|CIBERONC, 08035 Barcelona, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arribas
authors.affiliation: EurOPDX Consortium and are at the Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.affiliation: EurOPDX Consortium and are at Cancer Research UK Cambridge Institute, Cambridge Cancer Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Bruna
authors.affiliation: 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.
authors.forename: Eva
authors.initials: E
authors.lastname: Budinská
authors.affiliation: EurOPDX Consortium and are at Cancer Research UK Cambridge Institute, Cambridge Cancer Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.affiliation: EurOPDX Consortium and are at the Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
authors.affiliation: Hubrecht Institute, University Medical Centre Utrecht, and Princess Maxima Center for Pediatric Oncology, 3584CT Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: EurOPDX Consortium and are at Lausanne Branch, Ludwig Institute for Cancer Research at the University of Lausanne, 1066 Lausanne, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.affiliation: 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.
authors.forename: Virginie
authors.initials: V
authors.lastname: Dangles-Marie
authors.affiliation: University of Colorado Cancer Center, Aurora, Colorado 80045, USA.
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
authors.affiliation: EurOPDX Consortium and is at the Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute IDIBELL, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Suarez
authors.affiliation: EurOPDX Consortium and are at the Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Hermans
authors.affiliation: EurOPDX Consortium and is at Beth Israel Deaconess Medical Center, Boston, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.affiliation: EurOPDX Consortium and are at the Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Jarzabek
authors.affiliation: EurOPDX Consortium and is at the University Medical Centre Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: de Jong
authors.affiliation: EurOPDX Consortium and are at The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Jonkers
authors.affiliation: EurOPDX Consortium and are at The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Kristel
authors.initials: K
authors.lastname: Kemper
authors.affiliation: EurOPDX Consortium and are at the Department of Experimental Oncology, European Institiute of Oncology, 20139 Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lanfrancone
authors.affiliation: EurOPDX Consortium and are at Oslo University Hospital, Institute for Cancer Research, 0424 Oslo, Norway.
authors.forename: Gunhild Mari
authors.initials: GM
authors.lastname: Mælandsmo
authors.affiliation: EurOPDX Consortium and are at Institut Curie, PSL Research University, Translational Research Department, 75005 Paris, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marangoni
authors.affiliation: 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.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
authors.affiliation: EurOPDX Consortium and are at the Candiolo Cancer Institute IRCCS and Department of Oncology, University of Torino, 10060 Candiolo, Torino, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.affiliation: EurOPDX Consortium and are at Oslo University Hospital, Institute for Cancer Research, 0424 Oslo, Norway.
authors.forename: Jens Henrik
authors.initials: JH
authors.lastname: Norum
authors.affiliation: EurOPDX Consortium and are at the Vall d'Hebron Institute of Oncology and CIBERONC, 08035 Barcelona, Spain.
authors.forename: Héctor G
authors.initials: HG
authors.lastname: Palmer
authors.affiliation: EurOPDX Consortium and are at The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Peeper
authors.affiliation: EurOPDX Consortium and are at the Department of Experimental Oncology, European Institiute of Oncology, 20139 Milan, Italy.
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.affiliation: EurOPDX Consortium and are at the Vall d'Hebron Institute of Oncology and CIBERONC, 08035 Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Piris-Gimenez
authors.affiliation: EurOPDX Consortium and are at Institut Curie, PSL Research University, Translational Research Department, 75005 Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: EurOPDX Consortium and are at Cancer Research UK Cambridge Institute, Cambridge Cancer Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Rueda
authors.affiliation: 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.|CIBERONC, 08035 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Seoane
authors.affiliation: EurOPDX Consortium and are at the Vall d'Hebron Institute of Oncology and CIBERONC, 08035 Barcelona, Spain.
authors.forename: Violeta
authors.initials: V
authors.lastname: Serra
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Soucek
authors.affiliation: EurOPDX Consortium and are at Lausanne Branch, Ludwig Institute for Cancer Research at the University of Lausanne, 1066 Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vanhecke
authors.affiliation: 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.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Seeding Science SAS, 75020 Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vinolo
authors.affiliation: EurOPDX Consortium and are at the Candiolo Cancer Institute IRCCS and Department of Oncology, University of Torino, 10060 Candiolo, Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bertotti
authors.affiliation: EurOPDX Consortium and are at the Candiolo Cancer Institute IRCCS and Department of Oncology, University of Torino, 10060 Candiolo, Torino, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Trusolino
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000502:physiology; D057285:Precision Medicine; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor