XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients.
Simonetta Maria LetoElena GrassiMarco AvolioValentina VurchioFrancesca CottinoMartina FerriEugenia R ZanellaSofia BorgatoGiorgio CortiLaura di BlasioDesiana SomaleMarianela Vara-MesslerFrancesco GalimiFrancesco SassiBarbara LupoIrene CatalanoMarika PinnelliMarco VivianiLuca SpertiAlfredo MellanoAlessandro FerreroCaterina C ZingarettiAlberto PuliafitoLuca PrimoAndrea BertottiLivio TrusolinoPublished in: Nature communications (2024)
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.
Keyphrases
- small cell lung cancer
- epidermal growth factor receptor
- drug discovery
- tyrosine kinase
- squamous cell carcinoma
- public health
- papillary thyroid
- clinical trial
- locally advanced
- metastatic colorectal cancer
- single cell
- randomized controlled trial
- genome wide
- wild type
- copy number
- risk assessment
- metabolic syndrome
- radiation therapy
- weight loss
- young adults
- lymph node metastasis
- psychometric properties
- single molecule
- cell therapy