Current Therapeutic Advances Targeting EGFR and EGFRvIII in Glioblastoma

Epidermal growth factor receptor (EGFR) and EGFRvIII analysis is of current interest in glioblastoma - the most common malignant primary CNS tumor, because of new EGFRvIII vaccine trials underway. EGFR activation in glioblastoma promotes cellular proliferation via activation of MAPK and PI3K-Akt pathways, and EGFRvIII is the most common variant, leading to constitutively active EGFR. This review explains EGFR and EGFRvIII signaling in GBM; describes targeted therapy approaches to date including tyrosine kinase inhibitor, antibody-based therapies, vaccines and pre-clinical RNA-based therapies, and discusses the difficulties encountered with these approaches including pathway redundancy and intratumoral heterogeneity.