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XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients

Author

Listed:
  • Simonetta M. Leto

    (Candiolo Cancer Institute – FPO IRCCS)

  • Elena Grassi

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Marco Avolio

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Valentina Vurchio

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Francesca Cottino

    (Candiolo Cancer Institute – FPO IRCCS)

  • Martina Ferri

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Eugenia R. Zanella

    (Candiolo Cancer Institute – FPO IRCCS)

  • Sofia Borgato

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Giorgio Corti

    (University of Torino)

  • Laura Blasio

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Desiana Somale

    (Candiolo Cancer Institute – FPO IRCCS
    an Evotec Company)

  • Marianela Vara-Messler

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino
    Sanofi Belgium)

  • Francesco Galimi

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Francesco Sassi

    (Candiolo Cancer Institute – FPO IRCCS)

  • Barbara Lupo

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Irene Catalano

    (Candiolo Cancer Institute – FPO IRCCS)

  • Marika Pinnelli

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Marco Viviani

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Luca Sperti

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Alfredo Mellano

    (Candiolo Cancer Institute – FPO IRCCS)

  • Alessandro Ferrero

    (Mauriziano Umberto I Hospital)

  • Caterina C. Zingaretti

    (Mauriziano Umberto I Hospital)

  • Alberto Puliafito

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Luca Primo

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Andrea Bertotti

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

  • Livio Trusolino

    (Candiolo Cancer Institute – FPO IRCCS
    University of Torino)

Abstract

The breadth and depth at which cancer models are interrogated contribute to the successful clinical translation of drug discovery efforts. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, where experimental therapies are typically tested. Here we introduce XENTURION, an open-science resource offering a platform of 128 PDX models from patients with metastatic CRC, along with matched PDX-derived tumoroids. Multidimensional omics analyses indicate that tumoroids retain extensive molecular fidelity with parental PDXs. A tumoroid-based trial with the anti-EGFR antibody cetuximab reveals variable sensitivities that are consistent with clinical response biomarkers, mirror tumor growth changes in matched PDXs, and recapitulate EGFR genetic deletion outcomes. Inhibition of adaptive signals upregulated by EGFR blockade increases the magnitude of cetuximab response. These findings illustrate the potential of large living biobanks, providing avenues for molecularly informed preclinical research in oncology.

Suggested Citation

  • Simonetta M. Leto & Elena Grassi & Marco Avolio & Valentina Vurchio & Francesca Cottino & Martina Ferri & Eugenia R. Zanella & Sofia Borgato & Giorgio Corti & Laura Blasio & Desiana Somale & Marianela, 2024. "XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51909-2
    DOI: 10.1038/s41467-024-51909-2
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    as
    1. Enzo Medico & Mariangela Russo & Gabriele Picco & Carlotta Cancelliere & Emanuele Valtorta & Giorgio Corti & Michela Buscarino & Claudio Isella & Simona Lamba & Barbara Martinoglio & Silvio Veronese &, 2015. "The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    2. Jesse S. Boehm & Mathew J. Garnett & David J. Adams & Hayley E. Francies & Todd R. Golub & William C. Hahn & Francesco Iorio & James M. McFarland & Leopold Parts & Francisca Vazquez, 2021. "Cancer research needs a better map," Nature, Nature, vol. 589(7843), pages 514-516, January.
    3. Daniela Bakula & Amelie J. Müller & Theresia Zuleger & Zsuzsanna Takacs & Mirita Franz-Wachtel & Ann-Katrin Thost & Daniel Brigger & Mario P. Tschan & Tancred Frickey & Horst Robenek & Boris Macek & T, 2017. "WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy," Nature Communications, Nature, vol. 8(1), pages 1-18, August.
    4. Andrea Bertotti & Eniko Papp & Siân Jones & Vilmos Adleff & Valsamo Anagnostou & Barbara Lupo & Mark Sausen & Jillian Phallen & Carolyn A. Hruban & Collin Tokheim & Noushin Niknafs & Monica Nesselbush, 2015. "The genomic landscape of response to EGFR blockade in colorectal cancer," Nature, Nature, vol. 526(7572), pages 263-267, October.
    5. Hua Sun & Song Cao & R. Jay Mashl & Chia-Kuei Mo & Simone Zaccaria & Michael C. Wendl & Sherri R. Davies & Matthew H. Bailey & Tina M. Primeau & Jeremy Hoog & Jacqueline L. Mudd & Dennis A. Dean & Raj, 2021. "Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    6. Fiona M. Behan & Francesco Iorio & Gabriele Picco & Emanuel Gonçalves & Charlotte M. Beaver & Giorgia Migliardi & Rita Santos & Yanhua Rao & Francesco Sassi & Marika Pinnelli & Rizwan Ansari & Sarah H, 2019. "Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens," Nature, Nature, vol. 568(7753), pages 511-516, April.
    7. Philip D. Dunne & Matthew Alderdice & Paul G. O'Reilly & Aideen C. Roddy & Amy M. B. McCorry & Susan Richman & Tim Maughan & Simon S. McDade & Patrick G. Johnston & Daniel B. Longley & Elaine Kay & Da, 2017. "Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    8. Fran Supek & Matko Bošnjak & Nives Škunca & Tomislav Šmuc, 2011. "REVIGO Summarizes and Visualizes Long Lists of Gene Ontology Terms," PLOS ONE, Public Library of Science, vol. 6(7), pages 1-9, July.
    9. James M. McFarland & Zandra V. Ho & Guillaume Kugener & Joshua M. Dempster & Phillip G. Montgomery & Jordan G. Bryan & John M. Krill-Burger & Thomas M. Green & Francisca Vazquez & Jesse S. Boehm & Tod, 2018. "Improved estimation of cancer dependencies from large-scale RNAi screens using model-based normalization and data integration," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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