Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib

Background: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (also known as Tarceva or OSI-774) has shown promising response rates in malignant gliomas. We investigated the association between expression of EGFR and downstream signaling components and the response of malignant gliomas to erlotinib in a phase I trial of erlotinib administered either alone or with the alkylating agent temozolomide. Methods: Expression of EGFR and ligand-independent EGFRvIII mutant proteins and of phos-phorylated protein kinase B (PKB)/Akt in specimens from glioma patients were assessed by immunohistochemistry. EGFR gene amplifi cation was evaluated by fl uorescence in situ hybridization. Mutations in PTEN and EGFR were assessed by polymerase chain reaction amplifi cation and sequencing. Response was evaluated by sequential magneti