Remarkably, the inhibition of leptin signaling via leptin peptide receptor antagonist 2 (LPrA2) significantly reduced VEGF/VEGFR2 expression and angiogenesis in human xenografts, estrogen responsive, MCF-7 and non-responsive, MDA-MB231-triple negative breast cancer cells, and mouse mammary tumors. The gene discussed is KDR; the disease is breast cancer.