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
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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