Communications Biology (Sep 2023)

A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

  • Maria Eugénia Marques Da Costa,
  • Sakina Zaidi,
  • Jean-Yves Scoazec,
  • Robin Droit,
  • Wan Ching Lim,
  • Antonin Marchais,
  • Jerome Salmon,
  • Sarah Cherkaoui,
  • Raphael J. Morscher,
  • Anouchka Laurent,
  • Sébastien Malinge,
  • Thomas Mercher,
  • Séverine Tabone-Eglinger,
  • Isabelle Goddard,
  • Francoise Pflumio,
  • Julien Calvo,
  • Francoise Redini,
  • Natacha Entz-Werlé,
  • Aroa Soriano,
  • Alberto Villanueva,
  • Stefano Cairo,
  • Pascal Chastagner,
  • Massimo Moro,
  • Cormac Owens,
  • Michela Casanova,
  • Raquel Hladun-Alvaro,
  • Pablo Berlanga,
  • Estelle Daudigeos-Dubus,
  • Philippe Dessen,
  • Laurence Zitvogel,
  • Ludovic Lacroix,
  • Gaelle Pierron,
  • Olivier Delattre,
  • Gudrun Schleiermacher,
  • Didier Surdez,
  • Birgit Geoerger

DOI
https://doi.org/10.1038/s42003-023-05320-0
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 15

Abstract

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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.