The EGFRvIII variant in glioblastoma multiforme.
Glioblastoma multiforme (GBM) is the most common brain tumour and has the worst prognosis. Epidermal growth factor receptor (EGFR) gene amplification, mutation and re-arrangement (all of which enhance tumour growth, survival, progression and resistance to therapy) are frequently observed in primary GBM. The most common EGFR variant in GBM, the EGFRvIII, is characterised by a deletion of 267 amino acids in the extracellular domain, leading to a receptor which is unable to bind ligand yet is constitutively active. Together with its impaired internalisation and degradation, the EGFRvIII enhances the tumourigenic potential of GBM by activating and sustaining mitogenic, anti-apoptotic and pro-invasive signalling pathways. This EGFRvIII-mediated enhanced tumourigenicity combined with the lack of EGFRvIII expression in normal tissue makes it an ideal candidate for targeted therapy. This review summarizes the current knowledge about the role of EGFRvIII in GBM and discusses therapeutic agents targeting EGFRvIII that are being evaluated as treatments for GBM.
Gan
Hui K
HK
Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Canada.
Kaye
Andrew H
AH
Luwor
Rodney B
RB