Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with

Background. The treatment efficacyof epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors like erlotinib has not met expectations for glioblastoma therapy, even for EGFR-overexpressing tumors. We de-termined possible mechanisms of therapy resistance using the unique BS153 glioblastoma cell line, which has retained amplification of the egfr gene and expression of EGFR variant (v)III. Methods. Functional effects of erlotinib, gefitinib, and cetuximab on BS153 proliferation, migration, and EGFR-dependent signal transductionwere systematically compared in vitro. The tumor-initiating capacity of pa-rental and treatment-resistant BS153 was studied in Naval Medical Research Institute/Foxn1nu mice. Potential mediators of resistance were knocked dow