VEGFA and central nervous system cancer: For example, hypoxia in the tumor microenvironment (TME) upregulates HIF-1α, which promotes the conversion of macrophages to the M2 type; the subsequent secretion of vascular endothelial growth factor (VEGF) further enhances glioma progression and temozolomide resistance via the PI3K/Akt/Nrf2 pathway (255).