Linked Life Data

21430781

Source:http://linkedlifedata.com/resource/pubmed/id/21430781

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7339
pubmed:dateCreated
2011-3-24
pubmed:abstractText
Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-?B pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-?B through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of I?B (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-?B enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-?B inhibitor I?B predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-?B as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
471
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
523-6
pubmed:dateRevised
2011-5-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
FAS and NF-?B signalling modulate dependence of lung cancers on mutant EGFR.
pubmed:affiliation
Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't