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

Authors

  • M. Schütte
  • T. Risch
  • N. Abdavi-Azar
  • K. Boehnke
  • D. Schumacher
  • M. Keil
  • R. Yildiriman
  • C. Jandrasits
  • T. Borodina
  • V. Amstislavskiy
  • C.L. Worth
  • C. Schweiger
  • S. Liebs
  • M. Lange
  • H.J. Warnatz
  • L.M. Butcher
  • J.E. Barrett
  • M. Sultan
  • C. Wierling
  • N. Golob-Schwarzl
  • S. Lax
  • S. Uranitsch
  • M. Becker
  • Y. Welte
  • J.L. Regan
  • M. Silvestrov
  • I. Kehler
  • A. Fusi
  • T. Kessler
  • R. Herwig
  • U. Landegren
  • D. Wienke
  • M. Nilsson
  • J.A. Velasco
  • P. Garin-Chesa
  • C. Reinhard
  • S. Beck
  • R. Schäfer
  • C.R.A. Regenbrecht
  • D. Henderson
  • B. Lange
  • J. Haybaeck
  • U. Keilholz
  • J. Hoffmann
  • H. Lehrach
  • M.L. Yaspo

Journal

  • Nature Communications

Citation

  • Nat Commun 8: 14262

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.


DOI

doi:10.1038/ncomms14262