• Medientyp: E-Artikel
  • Titel: Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
  • Beteiligte: Schütte, Moritz; Risch, Thomas; Abdavi-Azar, Nilofar; Boehnke, Karsten; Schumacher, Dirk; Keil, Marlen; Yildiriman, Reha; Jandrasits, Christine; Borodina, Tatiana; Amstislavskiy, Vyacheslav; Worth, Catherine L.; Schweiger, Caroline; Liebs, Sandra; Lange, Martin; Warnatz, Hans- Jörg; Butcher, Lee M.; Barrett, James E.; Sultan, Marc; Wierling, Christoph; Golob-Schwarzl, Nicole; Lax, Sigurd; Uranitsch, Stefan; Becker, Michael; Welte, Yvonne; [...]
  • Erschienen: Springer Science and Business Media LLC, 2017
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/ncomms14262
  • ISSN: 2041-1723
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 &gt;4,000 assays testing 16 clinical drugs on patient-derived <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic> 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 <jats:italic>RAS/RAF</jats:italic> mutations in predicting sensitivity to the EGFR inhibitor cetuximab.</jats:p>
  • Zugangsstatus: Freier Zugang