Biomarkers for glioblastoma multiforme: status quo

Glioblastoma (GBM) is the most frequent and most malignant central nervous system (CNS) tumor. GBM shows poor prognosis with a median overall survival of 14.6 months, despite current surgical and adjuvant therapies. O(6)-methylguanine-DNA methyltransferase (MGMT) methylation is the strongest molecular prognosticator for GBM with therapeutic implications in adjuvant treatment. Isocitrate dehydrogenase (IDH) mutation is the most recently introduced molecular marker and is important for the GBM classification because distinguishes primary (de novo) from secondary GBM. In the last two decades huge advances in the understanding of biopathological bases of gliomagenesis have been made but, to date, there is a lack of biopathological markers endowed of some prognostic and predictive value for GBM.

In the present review we analyzed the role, as possible prognosticators, of epidermal growth factor receptor (EGFR) variant III (EGFRvIII), phosphatase and tensin homolog (PTEN) deletion and other alteration of the receptor tyrosine kinase (RTK) pathway, and vascular endothelial growth factor (VEGF) expression. We included in the review studies considering both the prognostic value and the predictive value for response to therapy of the above-mentioned biomarkers.

These factors have a paramount importance in gliomagenesis and are potential targets for individualized therapies. EGFR can be targeted by tyrosine kinase inhibitors (TKIs). mTOR, whose activation is triggered by PTEN loss, is the target of rapalogs and VEGF is the target of the molecular antibody bevacizumab. Unfortunately, current evidence is insufficient to draw a definite prognostic/predictive role for these biomarkers in GBM. Further understanding the gliomagenesis pathways and looking for biomarkers endowed with translational relevance are necessary efforts in order to find the appropriate, tailored therapy for each specific GBM patient.