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Dissection of the molecular complexity of colorectal cancer in pre-clinical models identifies predictive signatures of sensitivity to EGFR inhibitors

Colorectal carcinoma (CRC) is a heterogeneous tumour entity, with only a fraction of the tumours responding to currently available therapies. A detailed understanding of the biology and genetics of CRC is a prerequisite for precision medicine. To address this challenge in clinical oncology, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed an integrated pre-clinical platform analysing drug sensitivity in the established matched patient-derived in vivo and in vitro models, 46 three-dimensional cell cultures and 59 xenografts, recapitulating many of the molecular features of the donor tumours. We generated extensive omics information on patient tumours and their derived models used to generate a compendium of drug sensitivity data. We could distinguish tumour molecular sub-groups responding differently to therapy and identified a novel independent predictor of sensitivity to the EGFR inhibitor cetuximab. The findings reported here will advance our understanding of CRC and its response to therapy.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001002072 Illumina HiSeq 2000 23
EGAD00001002073 Illumina HiSeq 2000 12
EGAD00001002074 Illumina HiSeq 2000 3
EGAD00001002075 Illumina HiSeq 2000 1
EGAD00001002076 Illumina HiSeq 2000 19
EGAD00001002077 Illumina HiSeq 2000 87
EGAD00001002078 Illumina HiSeq 2000 28
EGAD00001002079 Illumina HiSeq 2000 1
EGAD00001002080 Illumina HiSeq 2000 37
EGAD00001002081 Illumina HiSeq 2000 4
EGAD00001002082 Illumina HiSeq 2000 69
EGAD00001002083 Illumina HiSeq 2000 2
EGAD00001002084 Illumina HiSeq 2000 23
EGAD00001002085 Illumina HiSeq 2000 12
EGAD00001002086 Illumina HiSeq 2000 1
EGAD00001002087 Illumina HiSeq 2000 19
EGAD00001002088 Illumina HiSeq 2000 87
EGAD00001002089 Illumina HiSeq 2000 25
EGAD00001002090 Illumina HiSeq 2000 1
EGAD00001002091 Illumina HiSeq 2000 38
EGAD00001002092 Illumina HiSeq 2000 5
EGAD00001002093 Illumina HiSeq 2000 33
EGAD00001002094 Illumina HiSeq 2000 2
EGAD00001002095 Illumina HiSeq 2000 14
EGAD00001002096 Illumina HiSeq 2000 12
EGAD00001002097 Illumina HiSeq 2000 1
EGAD00001002098 Illumina HiSeq 2000 19
EGAD00001002099 Illumina HiSeq 2000 55
EGAD00001002100 Illumina HiSeq 2000 25
EGAD00001002101 Illumina HiSeq 2000 1
EGAD00001002102 Illumina HiSeq 2000 38
EGAD00001002103 Illumina HiSeq 2000 5
EGAD00001002104 AB 5500xl Genetic Analyzer 76
EGAD00001002105 AB 5500xl Genetic Analyzer AB 5500xl-W Genetic Analysis System 16
EGAD00001002106 AB 5500xl Genetic Analyzer 1
EGAD00001002107 AB 5500xl Genetic Analyzer AB 5500xl-W Genetic Analysis System 66
EGAD00001002883 Illumina HiSeq 2000 60
EGAD00001002884 Illumina HiSeq 2000 8
EGAD00001003362 Illumina HiSeq 2000 49
EGAD00001003363 Illumina HiSeq 2000 114
EGAD00001003364 Illumina HiSeq 2000 4
EGAD00001003365 Illumina HiSeq 2000 1
EGAD00001003366 Illumina HiSeq 2000 10
EGAD00001003367 Illumina HiSeq 2000 7
EGAD00001003368 Illumina HiSeq 2000 1
EGAD00001003369 Illumina HiSeq 2000 13
EGAD00001003370 Illumina HiSeq 2000 10
EGAD00001003371 Illumina HiSeq 2000 1
EGAD00001003372 Illumina HiSeq 2000 4
EGAD00001003373 Illumina HiSeq 2000 1
EGAD00001003374 Illumina HiSeq 2000 8
EGAD00001003375 Illumina HiSeq 2000 7
EGAD00001003376 Illumina HiSeq 2000 12
EGAD00001003377 Illumina HiSeq 2000 10
EGAD00001003378 Illumina HiSeq 2000 1
EGAD00001003379 Illumina HiSeq 2000 4
EGAD00001003380 Illumina HiSeq 2000 1
EGAD00001003381 Illumina HiSeq 2000 10
EGAD00001003383 Illumina HiSeq 2000 7
EGAD00001003384 Illumina HiSeq 2000 14
EGAD00001003385 AB 5500 Genetic Analyzer 1
EGAD00001003386 AB 5500 Genetic Analyzer 1
EGAD00010001161 Illumina 450K 15
EGAD00010001162 Illumina 450K 67
Publications Citations
Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors.
Nat Commun 8: 2017 14262
180
Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data.
Cancers (Basel) 13: 2021 6018
2
A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer.
Mol Cancer 22: 2023 89
3