The Complexities of Resistance to Bevacizumab

Glioblastoma is a highly malignant primary tumor of the central nervous system tumor with a poor survival rate. The treatment of glioblastoma is shifting from a purely cytotoxic approach to one that incorporates anti-angiogenic agents. Bevacizumab (Avastin; Roche) was approved in the United States for the treatment of recurrent glioblastoma in May 2009 and showed encouraging results. However, “rebound” tumor progression with accelerated clinical decline has been observed after cessation of bevacizumab therapy in patients with high-grade gliomas and there is no effective treatment for the recurrent glioblastoma after bevacizumab failure. This review summarizes the characteristics of glioblastoma as well as the possible mechanisms of recurrence after anti-angiogenic therapy. Furthermore, alterations of the key molecular pathways and glycometabolic remodeling in glioblastoma are also discussed within. A better understanding of the complexities underpinning the resistance to bevacizumab and the combination of targeting cancer metabolism and anti-VEGF therapy may ultimately result in new modes of treatment, which hopefully improve the overall survival for patients diagnosed with glioblastoma.