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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5687
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pubmed:dateCreated |
2004-8-24
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pubmed:abstractText |
Gefitinib (Iressa, Astra Zeneca Pharmaceuticals) is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor (EGFR) and induces dramatic clinical responses in nonsmall cell lung cancers (NSCLCs) with activating mutations within the EGFR kinase domain. We report that these mutant EGFRs selectively activate Akt and signal transduction and activator of transcription (STAT) signaling pathways, which promote cell survival, but have no effect on extracellular signal-regulated kinase signaling, which induces proliferation. NSCLC cells expressing mutant EGFRs underwent extensive apoptosis after small interfering RNA-mediated knockdown of the mutant EGFR or treatment with pharmacological inhibitors of Akt and STAT signaling and were relatively resistant to apoptosis induced by conventional chemotherapeutic drugs. Thus, mutant EGFRs selectively transduce survival signals on which NSCLCs become dependent; inhibition of those signals by gefitinib may contribute to the drug's efficacy.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/gefitinib
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1095-9203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
20
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pubmed:volume |
305
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1163-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15284455-Animals,
pubmed-meshheading:15284455-Antineoplastic Agents,
pubmed-meshheading:15284455-Apoptosis,
pubmed-meshheading:15284455-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:15284455-Catalytic Domain,
pubmed-meshheading:15284455-Cell Line,
pubmed-meshheading:15284455-Cell Line, Tumor,
pubmed-meshheading:15284455-Cell Survival,
pubmed-meshheading:15284455-DNA-Binding Proteins,
pubmed-meshheading:15284455-Enzyme Activation,
pubmed-meshheading:15284455-Humans,
pubmed-meshheading:15284455-Lung Neoplasms,
pubmed-meshheading:15284455-Mice,
pubmed-meshheading:15284455-Milk Proteins,
pubmed-meshheading:15284455-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15284455-Mutation,
pubmed-meshheading:15284455-Mutation, Missense,
pubmed-meshheading:15284455-Phosphorylation,
pubmed-meshheading:15284455-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15284455-Proto-Oncogene Proteins,
pubmed-meshheading:15284455-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15284455-Quinazolines,
pubmed-meshheading:15284455-RNA, Small Interfering,
pubmed-meshheading:15284455-Receptor, Epidermal Growth Factor,
pubmed-meshheading:15284455-STAT5 Transcription Factor,
pubmed-meshheading:15284455-Sequence Deletion,
pubmed-meshheading:15284455-Signal Transduction,
pubmed-meshheading:15284455-Trans-Activators,
pubmed-meshheading:15284455-Transfection,
pubmed-meshheading:15284455-Tyrosine
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pubmed:year |
2004
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pubmed:articleTitle |
Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways.
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pubmed:affiliation |
Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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