Further experiments indicated that both BIDEN-AP and its nanoconjugate CCPM-BIDEN-AP promoted forward, tumor-suppressive EphB4 signaling both in vitro and in vivo; blocked the reverse signaling by interfering in the interaction between EphB4 and its natural ligand EFNB2 in endothelial cells, thereby suppressing these cells’ angiogenic properties; and sensitized Bev-resistant endothelial cells to cell death. This evidence concerns the gene EPHB4 and neoplasm.