In:
Molecular Systems Biology, EMBO, Vol. 9, No. 1 ( 2013-01)
Abstract:
A ‘lung cancer’‐specific mutant EGFR interactome was generated by a global analysis of protein–protein interactions and phosphorylation. After functional screening, nine proteins were identified as essential for the viability of EGFR‐mutant lung cancer cells. image The interactome of lung cancer‐associated mutant forms of epidermal growth factor receptor (EGFR), consisting of 263 proteins, was built by integrating protein–protein interactions and tyrosine phosphorylation. Systematic perturbations of the network nodes revealed a core network of 14 proteins, 9 of which were shown to be specifically associated with survival of EGFR‐mutant lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors showed differential dependence on the core network proteins. A drug network associated with the core network proteins led to the identification of two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib.
Type of Medium:
Online Resource
ISSN:
1744-4292
,
1744-4292
Language:
English
Publisher:
EMBO
Publication Date:
2013
detail.hit.zdb_id:
2193510-5
SSG:
12
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