Schütte, M; Risch, T; Abdavi-Azar, N; Boehnke, K; Schumacher, D; Keil, M; Yildiriman, R; Jandrasits, C; Borodina, T; Amstislavskiy, V; Worth, CL; Schweiger, C; Liebs, S; Lange, M; Warnatz, HJ; Butcher, LM; Barrett, JE; Sultan, M; Wierling, C; Golob-Schwarzl, N; Lax, S; Uranitsch, S; Becker, M; Welte, Y; Regan, JL; Silvestrov, M; Kehler, I; Fusi, A; Kessler, T; Herwig, R; Landegren, U; Wienke, D; Nilsson, M; Velasco, JA; Garin-Chesa, P; Reinhard, C; Beck, S; Schäfer, R; Regenbrecht, CR; Henderson, D; Lange, B; Haybaeck, J; Keilholz, U; Hoffmann, J; Lehrach, H; Yaspo, ML.
Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors.
Nat Commun. 2017; 8:14262-14262
- Authors Med Uni Graz:
Schweiger Caroline Margarete
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.