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

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.; Schafer, R.; Regenbrecht, C. R.; Henderson, D.; Lange, B.; Haybaeck, J.; Keilholz, U.; Hoffmann, J.; Lehrach, H.; Yaspo, M. L.

doi:10.1038/ncomms14262

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

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Risch, T.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Abdavi Azar, N.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Jandrasits, C.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Amstislavskiy, V.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Worth, C. L.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Warnatz, H. J.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Sultan, M.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Herwig, R.
Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Lehrach, H.
Emeritus Group of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;
Alacris Theranostics GmbH, Fabeckstr. 60-62, D-14195 Berlin, Germany;
Dahlem Centre for Genome Research and Medical Systems Biology, Fabeckstr. 60-62, 14195 Berlin, Germany;

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Yaspo, M. L.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Schütte, M., Risch, T., Abdavi Azar, N., Boehnke, K., Schumacher, D., Keil, M., et al. (2017). Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors. Nature Communications, 8: 8:14262. doi:10.1038/ncomms14262.

Cite as: https://hdl.handle.net/21.11116/0000-0000-78CF-1

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.