VEGF is upregulated in GBM and stimulates abnormal proliferation of tumor vessels by activating the essential downstream signaling pathways, such as MAPK/ERK1/2, endothelial nitric oxide synthase (eNOS), as well as mTOR.144 Interestingly, vessel normalization increases tumor blood perfusion and contributes to improved GBM patient survival (NCT00305656).145. Here, NOS3 is linked to glioblastoma.