FLT4 and breast cancer: Maladjustment of VEGF-C-elicited signaling results in tumor metastasis, especially via lymphatic vessels.261–265 Lymphatic metastasis is a challenge for clinical treatment of tumors and is the cause of death for some cancers,266,267 such as breast cancer,268 lung cancer,269 and melanoma.270 Soluble VEGFR3,271,272 VEGF-C inhibitor,273 VEGFR3 antibodies,274 and VEGF-C siRNA275 have been used in the treatment of lymphatic metastasis.