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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. and Risch, T. and Abdavi-Azar, N. and Boehnke, K. and Schumacher, D. and Keil, M. and Yildiriman, R. and Jandrasits, C. and Borodina, T. and Amstislavskiy, V. and Worth, C.L. and Schweiger, C. and Liebs, S. and Lange, M. and Warnatz, H.J. and Butcher, L.M. and Barrett, J.E. and Sultan, M. and Wierling, C. and Golob-Schwarzl, N. and Lax, S. and Uranitsch, S. and Becker, M. and Welte, Y. and Regan, J.L. and Silvestrov, M. and Kehler, I. and Fusi, A. and Kessler, T. and Herwig, R. and Landegren, U. and Wienke, D. and Nilsson, M. and Velasco, J.A. and Garin-Chesa, P. and Reinhard, C. and Beck, S. and Schäfer, R. and Regenbrecht, C.R.A. and Henderson, D. and Lange, B. and Haybaeck, J. and Keilholz, U. and Hoffmann, J. and 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
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:8
Page Range:14262
Date:10 February 2017
Official Publication:https://doi.org/10.1038/ncomms14262
PubMed:View item in PubMed

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