Evolving strategies: future treatment of glioblastoma

Abstract

Despite recent advances, there remains an unmet need for more effective treatments for newly diagnosed and recurrent glioblastoma (GBM). While currently available alkylator-based and antiangiogenic agents provide some efficacy, novel antiangiogenic and antiglioma treatments that provide enhanced efficacy with improvements in overall survival, the potential to overcome drug resistance and decreased treatment-related toxicity are still needed. Although VEGF-directed angiogenesis is critical during GBM pathogenesis, alternative proangiogenic and glioma-promoting pathways also play a key role in tumor progression. This article reviews the limitations of current GBM treatment, the importance of angiogenic signaling pathways in GBM pathogenesis and the preliminary results of novel antiangiogenic-targeted treatments being evaluated in GBM. Therapies that inhibit multiple glioma signaling pathways, including angiogenesis, have the possibility for further improving outcome in GBM and may represent the best option for increasing overall survival.

Keywords::

• alkylator-based chemotherapy
• angiogenesis
• chemoradiotherapy
• cytotoxic agents
• GBM
• glioblastoma
• targeted therapy
• temozolomide
• vascular endothelial growth factor
• VEGF

Financial & competing interests disclosure

Marc Chamberlain is on the advisory board for Genentech/Roche, Schering-Plough/Merck and Lily, and on the speakers bureau for Genentech/Roche and Schering-Plough/Merck. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial support was provided by UL Prisco, PhD, and R Rozich, PhD, of PAREXEL, and was funded by Bristol-Myers Squibb.