XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients
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.
Authors
- Francesco Galimi (ORCID: https://orcid.org/0000-0002-5939-6922)
- Marco Avolio (ORCID: https://orcid.org/0000-0002-2822-8141)
- Marco Viviani (ORCID: https://orcid.org/0000-0003-4698-8870)
- Martina Ferri (ORCID: https://orcid.org/0000-0003-4010-8166)
- Luca Primo (ORCID: https://orcid.org/0000-0002-1294-0441)
- Valentina Vurchio (ORCID: https://orcid.org/0000-0002-8699-2164)
- Alfredo Mellano (ORCID: https://orcid.org/0000-0002-9090-5123)
- Irene Catalano (ORCID: https://orcid.org/0000-0002-3895-5860)
- Alessandro Ferrero (ORCID: https://orcid.org/0000-0003-1504-5810)
- Eugenia R. Zanella (ORCID: https://orcid.org/0000-0002-8036-3789)
- Simonetta M. Leto (ORCID: https://orcid.org/0000-0001-7580-6584)
- Andrea Bertotti (ORCID: https://orcid.org/0000-0001-8196-7608)
- Laura di Blasio (ORCID: https://orcid.org/0000-0002-1337-7654)
- Desiana Somale (ORCID: https://orcid.org/0000-0001-6819-5383)
- Caterina C. Zingaretti (ORCID: https://orcid.org/0000-0002-7845-4235)
- Livio Trusolino (ORCID: https://orcid.org/0000-0002-6379-3365)
- Elena Grassi (ORCID: https://orcid.org/0000-0003-1066-927X)
- Marianela Vara-Messler (ORCID: https://orcid.org/0000-0003-0493-7071)
- Giorgio Corti (ORCID: https://orcid.org/0000-0001-6379-4117)
- Marika Pinnelli (ORCID: https://orcid.org/0000-0002-3565-2493)
- Francesco Sassi (ORCID: https://orcid.org/0000-0002-4741-0408)
- Alberto Puliafito (ORCID: https://orcid.org/0000-0002-0096-1536)
- Francesca Cottino (ORCID: https://orcid.org/0000-0001-6715-1784)
- Sofia Borgato (ORCID: https://orcid.org/0000-0001-5835-7211)
- Barbara Lupo (ORCID: https://orcid.org/0000-0002-4383-6882)
- Luca Sperti
Institutions
- Ablynx (Belgium) (BE)
- Sanofi (Belgium) (BE)
- Aptuit (Italy) (IT)
- Candiolo Cancer Institute (IT)
- University of Turin (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1038/s41467-024-51909-2
- Citations
- 12
- Primary Topic
- Cancer Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.64
Funders
- Merck KGaA
- Cancer Research UK
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Horizon 2020 Framework Programme
- HORIZON EUROPE Framework Programme