Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 ('Iressa')

Baldassarre Stea, Ryan Falsey, Kerri Kislin, Jay Patel, Heather Glanzberg, Steven Carey, Aaron A. Ambrad, Emmanuelle Meuillet, Jesse D Martinez

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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 μM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5Gy 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.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalCancer Letters
Volume202
Issue number1
DOIs
Publication statusPublished - Dec 8 2003

    Fingerprint

Keywords

  • Brain tumors
  • Clonogenic assay
  • Glioblastoma
  • Ionizing radiation
  • ZD1839

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this