A new analysis approach of epidermal growth factor receptor pathway activation patterns provides insights into cetuximab resistance mechanisms in head and neck cancer

被引:2
作者
von der Heyde, Silvia [1 ]
Beissbarth, Tim [1 ]
机构
[1] Univ Med Ctr Gottingen, Dept Med Stat, D-37073 Gottingen, Germany
关键词
HNSCC; EGFR; cetuximab; drug resistance; matrix factorization; GSEA; pathway signature; ERBB RECEPTORS;
D O I
10.1186/1741-7015-10-43
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The pathways downstream of the epidermal growth factor receptor (EGFR) have often been implicated to play crucial roles in the development and progression of various cancer types. Different authors have proposed models in cell lines in which they study the modes of pathway activities after perturbation experiments. It is prudent to believe that a better understanding of these pathway activation patterns might lead to novel treatment concepts for cancer patients or at least allow a better stratification of patient collectives into different risk groups or into groups that might respond to different treatments. Traditionally, such analyses focused on the individual players of the pathways. More recently in the field of systems biology, a plethora of approaches that take a more holistic view on the signaling pathways and their downstream transcriptional targets has been developed. Fertig et al. have recently developed a new method to identify patterns and biological process activity from transcriptomics data, and they demonstrate the utility of this methodology to analyze gene expression activity downstream of the EGFR in head and neck squamous cell carcinoma to study cetuximab resistance. Please see related article: http://www.biomedcentral.com/1471-2164/13/160
引用
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页数:4
相关论文
共 20 条
[1]  
[Anonymous], 2011, R: A Language and Environment for Statistical Computing
[2]   Model-based gene set analysis for Bioconductor [J].
Bauer, Sebastian ;
Robinson, Peter N. ;
Gagneur, Julien .
BIOINFORMATICS, 2011, 27 (13) :1882-1883
[3]   Interpreting experimental results using gene ontologies [J].
Beissbarth, Tim .
DNA MICROARRAYS, PART B: DATABASES AND STATISTICS, 2006, 411 :340-352
[4]   Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma [J].
Fertig, Elana J. ;
Ren, Qing ;
Cheng, Haixia ;
Hatakeyama, Hiromitsu ;
Dicker, Adam P. ;
Rodeck, Ulrich ;
Considine, Michael ;
Ochs, Michael F. ;
Chung, Christine H. .
BMC GENOMICS, 2012, 13
[5]   CoGAPS: an R/C++ package to identify patterns and biological process activity in transcriptomic data [J].
Fertig, Elana J. ;
Ding, Jie ;
Favorov, Alexander V. ;
Parmigiani, Giovanni ;
Ochs, Michael F. .
BIOINFORMATICS, 2010, 26 (21) :2792-2793
[6]   EGFR-PI3K-AKT-mTOR signaling in head and neck squamous cell carcinomas: attractive targets for molecular-oriented therapy [J].
Freudlsperger, Christian ;
Burnett, Jeffrey R. ;
Friedman, Jay A. ;
Kannabiran, Vishnu R. ;
Chen, Zhong ;
Van Waes, Carter .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2011, 15 (01) :63-74
[7]   Nested effects models for learning signaling networks from perturbation data [J].
Froehlich, Holger ;
Tresch, Achim ;
Beissbarth, Tim .
BIOMETRICAL JOURNAL, 2009, 51 (02) :304-323
[8]   Regulation of Heparin-Binding EGF-Like Growth Factor by miR-212 and Acquired Cetuximab-Resistance in Head and Neck Squamous Cell Carcinoma [J].
Hatakeyama, Hiromitsu ;
Cheng, Haixia ;
Wirth, Pamela ;
Counsell, Ashley ;
Marcrom, Samuel R. ;
Wood, Carey Burton ;
Pohlmann, Paula R. ;
Gilbert, Jill ;
Murphy, Barbara ;
Yarbrough, Wendell G. ;
Wheeler, Deric L. ;
Harari, Paul M. ;
Guo, Yan ;
Shyr, Yu ;
Slebos, Robbert J. ;
Chung, Christine H. .
PLOS ONE, 2010, 5 (09) :1-13
[9]   ERBB receptors and cancer: The complexity of targeted inhibitors [J].
Hynes, NE ;
Lane, HA .
NATURE REVIEWS CANCER, 2005, 5 (05) :341-354
[10]   A quantitative protein interaction network for the ErbB receptors using protein microarrays [J].
Jones, RB ;
Gordus, A ;
Krall, JA ;
MacBeath, G .
NATURE, 2006, 439 (7073) :168-174