Pharmacoproteomic characterisation of human colon and rectal cancer

  • 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.
Metadaten
Author:Martin Frejno, Riccardo Zenezini Chiozzi, Mathias Wilhelm, Heiner Koch, Runsheng Zheng, Susan Kläger, Benjamin Ruprecht, Chen Meng, Karl Kramer, Anna Jarzab, Stephanie Heinzlmeir, Elaine Johnstone, Enric Domingo, David Kerr, Moritz Jesinghaus, Julia Slotta-Huspenina, Wilko WeichertGND, Stefan KnappORCiD, Stephan M. Feller, Bernhard Kuster
URN:urn:nbn:de:hebis:30:3-449947
DOI:https://doi.org/10.15252/msb.20177701
ISSN:1744-4292
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29101300
Parent Title (English):Molecular systems biology
Publisher:EMBO Press
Place of publication:Heidelberg
Document Type:Article
Language:English
Date of Publication (online):2017/11/09
Date of first Publication:2017/11/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/11/09
Tag:CPTAC; CRC65; drug response; patient stratification; proteomics
Volume:13
Issue:11, Art. 951
Page Number:15
First Page:1
Last Page:15
Note:
© 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.
HeBIS-PPN:428653871
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0