Targeting Vascular Endothelial Growth Factor in Neuroblastoma

Angiogenesis is critical to tumor growth and metastasis and is dependent on growth factors, such as vascular endothelial growth factor (VEGF). The most characterized angiogenic factor, VEGF is an endothelial cell mitogen and permeability factor that has been found to be overexpressed in almost all human cancers. In a number of tumor model systems, antagonism of the VEGF pathway results in inhibition of angiogenesis and tumor growth. Specifically, VEGF inhibition has been shown to suppress tumor growth, decrease microvasculature, and induce apoptosis of endothelial cells. This close relationship between hypoxia, angiogenesis, and tumor growth makes VEGF and VEGF receptors attractive targets for anti-neoplastic therapies. However, in neuroblastoma, a vascular, aggressive pediatric solid tumor, VEGF therapies has demonstrated limited success, which may be due to resistance. Identifying synergistic anti-angiogenic targets may improve efficacy of VEGF treatments in neurobasltoma. In this article, we review the state of VEGF-targeted therapies, the results of recent clinical trials, as well as the future of novel anti-VEGF therapeutics. We will follow this with a review of VEGF treatment in the aggressive, pediatric malignancy, neuroblastoma, and discuss combination therapy of VEGF treatments with chemotherapy and other molecular targeted drugs.