We sought to determine whether Dopamine D2 Receptor (D 2 R) agonists inhibit lung tumor progression and identify subpopulations of lung cancer patients that benefit most from D 2 R agonist therapy. We demonstrate D 2 R agonists abrogate lung tumor progression in syngeneic (LLC1) and human xenograft (A549) orthotopic murine models through inhibition of tumor angiogenesis and reduction of tumor infiltrating myeloid derived suppressor cells. Pathological examination of human lung cancer tissue revealed a positive correlation between endothelial D 2 R expression and tumor stage. Lung cancer patients with a smoking history exhibited greater levels of D 2 R in lung endothelium. Our results suggest D 2 R agonists may represent a promising individualized therapy for lung cancer patients with high levels of endothelial D 2 R expression and a smoking history.