TY  - JOUR
A1  - Frejno, Martin
A1  - Zenezini Chiozzi, Riccardo
A1  - Wilhelm, Mathias
A1  - Koch, Heiner
A1  - Zheng, Runsheng
A1  - Kläger, Susan
A1  - Ruprecht, Benjamin
A1  - Meng, Chen
A1  - Kramer, Karl
A1  - Jarzab, Anna
A1  - Heinzlmeir, Stephanie
A1  - Johnstone, Elaine
A1  - Domingo, Enric
A1  - Kerr, David
A1  - Jesinghaus, Moritz
A1  - Slotta-Huspenina, Julia
A1  - Weichert, Wilko
A1  - Knapp, Stefan
A1  - Feller, Stephan M.
A1  - Kuster, Bernhard
T1  - Pharmacoproteomic characterisation of human colon and rectal cancer
T2  - Molecular systems biology
N2  - Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome‐guided pre‐clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials.
KW  - CPTAC
KW  - CRC65
KW  - drug response
KW  - patient stratification
KW  - proteomics
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44994
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-449947
SN  - 1744-4292
N1  - © 2017 The Authors. License: This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
VL  - 13
IS  - 11, Art. 951
SP  - 1
EP  - 15
PB  - EMBO Press
CY  - Heidelberg
ER  -