EGFR inhibition using gefitinib is not active in neuroblastoma cell lines.

BACKGROUND: Inhibition of the epidermal growth factor receptor (EGFR), using a tyrosine kinase inhibitor such as gefitinib, was suggested to be a new treatment approach for neuroblastoma. MATERIAL AND METHODS: EGFR expression and gene mutation were studied by reversetranscriptase-polxmerase chain reacting, fluorescence-activated cell sorting and gene sequencing in six neuroblastoma cell lines. In vitro cytotoxicity of gefitinib 0.1-10 microM alone or in combination with topotecan, vincristine and 9-cis retinoic acid (9cisRA) was determined by MTT proliferation assay. RESULTS: EGFR overexpression and gene mutations were absent in all cell lines tested. Inhibition of cell viability of 62-85% was found at 10 microM gefitinib, concentrations that, however, can clinically not be reached. In addition, gefitinib increased inhibitory effects of topotecan, vincristine and RA by 10-15% . CONCLUSION: Our in vitro data do not support the use of gefitinib as monotherapy in neuroblastoma and its chemosensitizing effects appear minor.