VEGF is a primary regulator, and its expression increases with tumor grade, promoting vascular proliferation and tumor progression.198 VEGFR-1 and VEGFR-2 activation play distinct roles in GBM initiation and malignancy.199 The overexpression of VEGF and VEGFR-1 in low-grade astrocytomas is correlated with poor prognosis, indicating their potential as prognostic biomarkers.200 Angiogenic factors in GBM are regulated by oncogene activation, tumor suppressor loss, and hypoxia. This evidence concerns the gene KDR and glioblastoma.