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

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:	Schütte, M., Risch, T., Abdavi-Azar, N., Boehnke, K., Schumacher, D., Keil, M. ORCID: https://orcid.org/0000-0002-6009-9845, Yildiriman, R., Jandrasits, C., Borodina, T. ORCID: https://orcid.org/0000-0002-6978-016X, Amstislavskiy, V., Worth, C.L. ORCID: https://orcid.org/0000-0002-1796-9606, 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. ORCID: https://orcid.org/0000-0003-3880-1658, 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
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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