Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors

摘要: Colorectal carcinoma represents a heterogeneous entity, with only fraction of the tumours responding to available therapies, requiring better molecular understanding disease in precision oncology. To address this challenge, OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed pre-clinical platform generating compendium drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived vivo vitro models. This large biobank tumours, 35 organoids 59 xenografts, extensive omics comparing donor derived models provides resource for advancing our CRC. Models recapitulate many genetic transcriptomic features donors, but defined less complex sub-groups because loss human stroma. Linking profiles patterns identifies novel biomarkers, including signature outperforming RAS/RAF mutations predicting EGFR inhibitor cetuximab.