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

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Item Type:Article
Title:Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors.
Creators Name:Schütte, M., Risch, T., Abdavi-Azar, N., Boehnke, K., Schumacher, D., Keil, M., Yildiriman, R., Jandrasits, C., Borodina, T., Amstislavskiy, V., Worth, C.L., Schweiger, C., Liebs, S., Lange, M., Warnatz, H.J., Butcher, L.M., Barrett, J.E., Sultan, M., Wierling, C., Golob-Schwarzl, N., Lax, S., Uranitsch, S., Becker, M., Welte, Y., Regan, J.L., Silvestrov, M., Kehler, I., Fusi, A., Kessler, T., Herwig, R., Landegren, U., Wienke, D., Nilsson, M., Velasco, J.A., Garin-Chesa, P., Reinhard, C., Beck, S., Schäfer, R., Regenbrecht, C.R.A., Henderson, D., Lange, B., Haybaeck, J., Keilholz, U., Hoffmann, J., Lehrach, H. and Yaspo, M.L.
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.
Keywords:Cetuximab, Colorectal Neoplasms, Epidermal Growth Factor Receptor, Gene Expression Profiling, Immunological Antineoplastic Agents, Neoplastic Gene Expression Regulation, Tumor Biomarkers, Xenograft Model Antitumor Assays, Animals
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:14262
Date:10 February 2017
Official Publication:https://doi.org/10.1038/ncomms14262
PubMed:View item in PubMed

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