Epithelial membrane protein-1 is a biomarker of gefitinib resistance
Male
Gene Expression Profiling
Prostatic Neoplasms
Gefitinib
Receptors, Cell Surface
Xenograft Model Antitumor Assays
Neoplasm Proteins
3. Good health
Gene Expression Regulation, Neoplastic
Mice
03 medical and health sciences
0302 clinical medicine
Drug Resistance, Neoplasm
Carcinoma, Non-Small-Cell Lung
Models, Animal
Mutation
Biomarkers, Tumor
Quinazolines
Animals
Humans
Female
DOI:
10.1073/pnas.0502113102
Publication Date:
2005-08-09T00:33:51Z
AUTHORS (11)
ABSTRACT
We describe a molecular resistance biomarker to gefitinib, epithelial membrane protein-1 (EMP-1). Gefitinib is small-molecule inhibitor that competes for the ATP-binding site on EGF receptor (EGFR) and has been approved patients with advanced lung cancers. Treatment gefitinib resulted in clinical benefit patients, and, recently, heterozygous somatic mutations within EGFR catalytic domain have identified as correlate objective response gefitinib. However, limits utility of this therapeutic fraction responses are rare. aimed assess phenotype mechanism vivo xenograft models patient samples. generated gefitinib-resistance an adenocarcinoma model by serially passaging tumors nude mice presence until was acquired. EMP-1 surface whose expression correlated acquisition resistance. further lack complete or partial cancer samples well progression secondary independent gefitinib-sensitizing mutations. This report suggests role adhesion molecule, EMP-1, resistance, probable cross-talk between molecule signaling pathway.
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CITATIONS (74)
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