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.