VEGF ISOFORMS AS OUTCOME BIOMARKER FOR ANTI-ANGIOGENIC THERAPY IN RECURRENT GLIOBLASTOMA

The effectiveness of anti-angiogenic therapy in glioblastoma (GBM) is probably the most controversial topic in neuro-oncology. Results from recently completed clinical trials with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), are openly discordant(1-3) and in contrast with impressive previous evidence.(4) Furthermore, none of these studies succeeded to establish predictive biomarkers for response to bevacizumab, which are urgently needed.(3) Thus, a rethinking on the rationale for anti-angiogenic treatment in GBM is warranted. VEGF is the main regulator of angiogenesis in GBM and exists in several isoforms with different molecular weights and biologic properties.(5) Notably, bevacizumab binds to all VEGF isoforms. We aimed to test the hypothesis that each GBM tumor may synthesize a given spectrum of VEGF isoforms, and that the sensitivity to bevacizumab may depend on the relative amount of the various isoforms.