Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD 1839 ('Iressa')

Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes unregulated cell growth and inhibits apoptosis, is believed to contribute to clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the EGFR signalling pathways may offer an attractive therapeutic target to increase the cytotoxic effects of radiotherapy. We report the effects of ZD1839 ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In radiation survival experiments, 5 muM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5 Gy in the presence of ZD1839. Dose and schedule of drug administration in combination with radiation appeared to be a crucial element to obtain radiosensitization of the cells. These studies suggest novel therapeutic strategies in the treatment of GBM. (C) 2003 Elsevier Ireland Ltd. All rights reserved.