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Nat Commun ; 8: 14262, 2017 02 10.
Article in English | 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.


Subject(s)
Biomarkers, Tumor/genetics , Cetuximab/therapeutic use , Colorectal Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Xenograft Model Antitumor Assays , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , ErbB Receptors/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Mice , Middle Aged , Young Adult
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