Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
| Autor: | Catherine L. Worth, Vyacheslav Amstislavskiy, Yvonne Welte, Lee M. Butcher, Tatiana Borodina, Jens Hoffmann, Christoph Wierling, Christian R. A. Regenbrecht, Sandra Liebs, Caroline Schweiger, Moritz Schütte, Juan A. Velasco, Martin Lange, David Henderson, Marc Sultan, Johannes Haybaeck, Michael Becker, Maxine Silvestrov, Christoph Reinhard, Christine Jandrasits, Karsten Boehnke, Nicole Golob-Schwarzl, Sigurd Lax, Mats Nilsson, Marie-Laure Yaspo, Thomas Kessler, Reha Yildiriman, Ulrich Keilholz, Hans-Jörg Warnatz, Pilar Garin-Chesa, Stefan Uranitsch, Bodo Lange, Dirk Wienke, Nilofar Abdavi-Azar, Dirk Schumacher, Ralf Herwig, James E. Barrett, Stephan Beck, Inge Kehler, Thomas Risch, Alberto Fusi, Hans Lehrach, Ulf Landegren, Marlen Keil, Reinhold Schäfer, Joseph L. Regan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research Colorectal cancer Cetuximab General Physics and Astronomy Disease 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit Bioinformatics Mice Antineoplastic Agents Immunological EGFR inhibitors Aged 80 and over Multidisciplinary Middle Aged Biobank 3. Good health ErbB Receptors Gene Expression Regulation Neoplastic Colorectal Neoplasms medicine.drug Adult medicine.medical_specialty Adolescent Science Article General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences Stroma In vivo Internal medicine Biomarkers Tumor Genetics medicine Animals Humans Genetik Aged Cancer och onkologi business.industry Gene Expression Profiling General Chemistry medicine.disease Xenograft Model Antitumor Assays Gene expression profiling 030104 developmental biology Cancer and Oncology business |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-19 (2017) Nature Communications Schutte, 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 2017, ' Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors ', Nature Communications, vol. 8, 14262, pp. 1-19 . https://doi.org/10.1038/ncomms14262 |
| ISSN: | 2041-1723 |
| DOI: | 10.17169/refubium-24207 |
| Popis: | 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. The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response. |
| Databáze: | OpenAIRE |
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