Abstract

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.

A collection of 131 multi-panel pediatric tumor PDX models are generated and characterized in a comprehensive effort to provide support for basic and translational research and treatment development in advanced pediatric malignancies.

Details

Title
A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors
Author
Marques Da Costa, Maria Eugénia 1   VIAFID ORCID Logo  ; Zaidi, Sakina 2   VIAFID ORCID Logo  ; Scoazec, Jean-Yves 3   VIAFID ORCID Logo  ; Droit, Robin 4 ; Lim, Wan Ching 5 ; Marchais, Antonin 1 ; Salmon, Jerome 6 ; Cherkaoui, Sarah 7 ; Morscher, Raphael J. 7 ; Laurent, Anouchka 8 ; Malinge, Sébastien 9   VIAFID ORCID Logo  ; Mercher, Thomas 8 ; Tabone-Eglinger, Séverine 10   VIAFID ORCID Logo  ; Goddard, Isabelle 11 ; Pflumio, Francoise 12   VIAFID ORCID Logo  ; Calvo, Julien 12   VIAFID ORCID Logo  ; Redini, Francoise 13 ; Entz-Werlé, Natacha 14 ; Soriano, Aroa 15 ; Villanueva, Alberto 16   VIAFID ORCID Logo  ; Cairo, Stefano 17 ; Chastagner, Pascal 18 ; Moro, Massimo 19   VIAFID ORCID Logo  ; Owens, Cormac 20 ; Casanova, Michela 19 ; Hladun-Alvaro, Raquel 15 ; Berlanga, Pablo 21 ; Daudigeos-Dubus, Estelle 6   VIAFID ORCID Logo  ; Dessen, Philippe 4 ; Zitvogel, Laurence 6   VIAFID ORCID Logo  ; Lacroix, Ludovic 3 ; Pierron, Gaelle 22   VIAFID ORCID Logo  ; Delattre, Olivier 23   VIAFID ORCID Logo  ; Schleiermacher, Gudrun 24   VIAFID ORCID Logo  ; Surdez, Didier 25   VIAFID ORCID Logo  ; Geoerger, Birgit 1   VIAFID ORCID Logo 

1  Gustave Roussy Cancer Campus, Université Paris-Saclay, INSERM U1015, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535); Gustave Roussy Cancer Campus, Department of Pediatric and Adolescent Oncology, Villejuif, France (GRID:grid.14925.3b) (ISNI:0000 0001 2284 9388) 
2  PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, INSERM U830, Equipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645) 
3  Gustave Roussy Cancer Campus, Université Paris-Saclay, Department of Pathology and Laboratory Medicine, Translational Research Laboratory and Biobank, AMMICA, INSERM US23/CNRS UMS3655, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535) 
4  Gustave Roussy Cancer Campus, Université Paris-Saclay, INSERM U1015, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535); Bioinformatics Platform, AMMICA, INSERM US23/CNRS, Gustave Roussy Cancer Campus, Villejuif, France (GRID:grid.14925.3b) (ISNI:0000 0001 2284 9388) 
5  Gustave Roussy Cancer Campus, Université Paris-Saclay, INSERM U1015, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535); Perdana University, School of Data Sciences, Kuala Lumpur, Malaysia (GRID:grid.261834.a) (ISNI:0000 0004 1776 6926) 
6  Gustave Roussy Cancer Campus, Université Paris-Saclay, INSERM U1015, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535) 
7  Gustave Roussy Cancer Campus, Université Paris-Saclay, INSERM U1015, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535); University of Zurich, Division of Oncology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
8  Equipe labellisée Ligue Nationale Contre le Cancer, PEDIAC program, Gustave Roussy Cancer Campus, INSERM U1170, Université Paris-Saclay, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535) 
9  Equipe labellisée Ligue Nationale Contre le Cancer, PEDIAC program, Gustave Roussy Cancer Campus, INSERM U1170, Université Paris-Saclay, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535); Perth Children’s Hospital, Telethon Kids Institute – Cancer Centre, Nedlands, Australia (GRID:grid.518128.7) (ISNI:0000 0004 0625 8600) 
10  Centre Léon Bérard, Biological Ressources Center, Lyon, France (GRID:grid.418116.b) (ISNI:0000 0001 0200 3174) 
11  Claude Bernard Université Lyon 1, Small Animal Platform, Cancer Research Center of Lyon, INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Lyon, France (GRID:grid.7849.2) (ISNI:0000 0001 2150 7757) 
12  Université de Paris-Université Paris-Saclay, UMR-E008 Stabilité Génétique, Cellules Souches et Radiations, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Fontenay-aux-Roses, France (GRID:grid.7849.2) 
13  Université Nantes, INSERM UMR 1238, Nantes, France (GRID:grid.4817.a) (ISNI:0000 0001 2189 0784) 
14  University of Strasbourg, Faculty of Pharmacy, Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, Strasbourg, UMR CNRS 7021, team tumoral signaling and therapeutic targets, Illkirch, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291) 
15  Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Research Institute (VHIR), Childhood Cancer and Blood Disorders Research Group, Division of Pediatric Hematology and Oncology, Barcelona, Spain (GRID:grid.430994.3) (ISNI:0000 0004 1763 0287) 
16  Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet del Llobregat, Xenopat SL, Parc Cientific de Barcelona (PCB), Chemoresistance and Predictive Factors Group, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Oncobell Program, Barcelona, Spain (GRID:grid.418284.3) (ISNI:0000 0004 0427 2257) 
17  XenTech, Evry, France (GRID:grid.418284.3) 
18  Children University Hospital, Vandoeuvre‑lès‑Nancy, University of Nancy, Nancy, France (GRID:grid.29172.3f) (ISNI:0000 0001 2194 6418) 
19  Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (GRID:grid.417893.0) (ISNI:0000 0001 0807 2568) 
20  Children’s Health Ireland, Paediatric Haematology/Oncology, Crumlin, Republic of Ireland (GRID:grid.417322.1) (ISNI:0000 0004 0516 3853) 
21  Gustave Roussy Cancer Campus, Department of Pediatric and Adolescent Oncology, Villejuif, France (GRID:grid.14925.3b) (ISNI:0000 0001 2284 9388) 
22  Service d’oncogénétique, Institut Curie, Unité de Génétique Somatique, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384) 
23  PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, INSERM U830, Equipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); Service d’oncogénétique, Institut Curie, Unité de Génétique Somatique, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384); PSL Research University, Institut Curie, SiRIC RTOP (Recherche Translationnelle en Oncologie Pédiatrique); Translational Research Department, Institut Curie Research Center, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384) 
24  PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, INSERM U830, Equipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); PSL Research University, Institut Curie, SiRIC RTOP (Recherche Translationnelle en Oncologie Pédiatrique); Translational Research Department, Institut Curie Research Center, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384) 
25  PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, INSERM U830, Equipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); Balgrist University Hospital, University of Zurich, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
Pages
949
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-023-05320-0
ProQuest document ID
2865943846
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.