Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gefitinib (ZD1839, Iressa), a member of the 4-anilinoquinazoline class of compounds, has the chemical name 4-quinazolinamine, N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. Gefitinib often is referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor (EGFR). EGFR expression has been noted in neuroblastoma and rhabdomyosarcoma cell lines and in tumor specimens from children with Wilms tumor, osteosarcoma, and glioma. Thus, gefitinib, the first marketed EGFR tyrosine kinase inhibitor, was chosen for study in children with refractory solid tumors and central nervous system (CNS) malignancies. This review discusses findings from 3 clinical trials of gefitinib in children with refractory solid tumors and CNS malignancies, focusing on the clinical pharmacology of the compound. To date, gefitinib has been studied in children as a single agent and in combination with irinotecan. Overall, the compound has been well tolerated in children and has a safety profile similar to that observed in adults. The clinical pharmacokinetics of gefitinib in children are similar to those observed in adults. Finally, the future for the use of gefitinib in pediatrics is similar to that of other molecularly targeted agents and awaits definition of tumors and patient populations in which it will be most advantageous.
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PMID:Evaluation of gefitinib for treatment of refractory solid tumors and central nervous system malignancies in pediatric patients. 1680 60

We aimed to examine the expression of EGFR in neuroblastoma tissues and to investigate the antitumor activity of a selective EGFR-tyrosine kinase inhibitor, gefitinib, on neuroblastoma. The expression of EGFR was detected in each of two tumor tissues by immunohistochemistry and eight of 10 cell lines by Western blotting. Gefitinib inhibited EGFR-phosphorylation and in vitro cell growth (IC(50): approximately 1.2 microM), and a high concentration of gefitinib (20-30 microM) induced apoptosis in vitro. This is the first report that EGFR protein is expressed on the cell surface in neuroblastoma tissues and in cell lines. We also demonstrated an EGFR inhibitor induced apoptosis on neuroblastoma cells. Our results suggest the feasibility of targeting EGFR as a novel strategy against neuroblastoma.
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PMID:Induction of apoptosis by an inhibitor of EGFR in neuroblastoma cells. 1748 63