Therefore, reduced LVD observed with r84 and bevacizumab therapy is perhaps mechanistically similar to the reduction in LVD observed in 2C3-treated breast cancer xenografts, which correlated with a VEGFR2-mediated down regulation of VEGFR3 in lymphatic endothelial cells and a decrease in Ang-2 expression in endothelial cells and tumor cells [49]. This evidence concerns the gene FLT4 and breast carcinoma.