VEGFA and neoplasm: The causes of the EPR effect are (i) defective tumor blood vessels; (ii) various vascular effectors including nitric oxide (NO), bradykinin, vascular endothelial growth factor (VEGF), carbon monoxide (CO) produced by heme oxygenase-1 (HO-1), and prostaglandins (e.g., prostaglandin E2, prostaglandin I2) that facilitate extravasation; and (iii) impaired lymphatic clearance, so that macromolecular drugs remain in tumor tissues for extended periods [1,4,7,8,9,10].