Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors.
Nat Commun
; 8: 14262, 2017 02 10.
Article
em En
| MEDLINE
| ID: mdl-28186126
ABSTRACT
Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Biomarcadores Tumorais
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Ensaios Antitumorais Modelo de Xenoenxerto
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Receptores ErbB
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Cetuximab
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Animals
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article