Pre-treatment with a single dose of Pazopanib increased SDRT-induced ASMase activity and endothelial dysfunction in vitro and in vivo, enhancing SDRT tumor cure, and exhibiting critical dependence on timing relative to SDRT exposure, suggesting a mechanism of action identical to that demonstrated for anti-VEGF/VEGFR2 antibodies. Here, VEGFA is linked to endothelial dysfunction.