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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
Alacris Theranost GmbH, Fabeckstr 60-62, D-14195 Berlin, Germany..
Max Planck Inst Mol Genet, Dept Vertebrate Genom, Otto Warburg Lab Gene Regulat & Syst Biol Canc, Ihnestr 73, D-14195 Berlin, Germany..
Max Planck Inst Mol Genet, Dept Vertebrate Genom, Otto Warburg Lab Gene Regulat & Syst Biol Canc, Ihnestr 73, D-14195 Berlin, Germany..
Eli Lilly & Co, Lilly Res Labs, Quantitat Biol, Avda Ind 30, Madrid 28108, Spain..
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 14262Article in journal (Refereed) Published
Abstract [en]

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 44,000 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.

Place, publisher, year, edition, pages
2017. Vol. 8, article id 14262
National Category
Cancer and Oncology Genetics
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URN: urn:nbn:se:uu:diva-316929DOI: 10.1038/ncomms14262ISI: 000393656400001PubMedID: 28186126OAI: oai:DiVA.org:uu-316929DiVA, id: diva2:1079694
Funder
Swedish Research CouncilVINNOVAEU, European Research CouncilAvailable from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-11-29Bibliographically approved

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