Bevacizumab in Treatment of Glioblastoma: Recent Progress and Challenges

Grade IV glioma known as Glioblastoma multiforme (GBM); is the most malignant primary brain tumor in adults. Features of GBM include invasion, aggression and angiogenesis. GBM patients have median survival time of 14.6 months approximately, due to tumor recurrence. Common treatment is surgery followed by chemo radiation. Bevacizumab (BEV) is a recombinant humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF). It has been studied in both recurrent and newly diagnosed GBM but, it isapproved by U.S. Food and Drug Administration only for improving recurrent GBM patients. Main function of BEV is its antiangiogenic effect. A retrospective cohort study have indicated that use of angiotensin system inhibitors (ASI) or calcium antagonists with BEVtherapy could be effective for recurrent GBM treatment. BEV with concomitant Temozolomide and radiotherapy was shown to prolong progression-free survival in also newly diagnosed GBM patients. Available documents signify that BEV treatment increased glioma invasionand made them more resistant so because of upregulation of metalloproteinase activity, a crucial regulator of GBM invasion, the tumor relapse after BEV therapy is represented as a non-enhancing infiltrative phenotype in the radiographic imaging. Recent studies signified that δ-catenin is resulting BEV-induced glioma cell invasions; some others showed that stimulation of protein kinase B (AKT), a serine-threonine kinase is also implicated in it. Available documents signify that the combination of BEV with an integrin inhibitor (Cilengitide) suppressedthe integrin-mediated cell adhesion pathway as an underlying mechanism of its anti-invasive effect so it exerted a significant anti-invasive effect. Conclusion: These findings like therapeutic targeting of AKT signal and δ-catenin or use of cilengitide could be the subjectof further researches for new methods of treatment.