Combined therapy with a Smad7 agonist—asiatic acid (10 mg/kg/day intraperitoneally (i.p.)for 4 weeks)—and a Smad3 inhibitor—naringenin (50 mg/kg/day i.p. for 4 weeks)—restored the balance between Smad3 and Smad7 signaling in the TGF-β-rich tumor microenvironment and significantly suppressed tumor invasion and metastasis in mouse models of melanoma and lung carcinoma [92]. This evidence concerns the gene SMAD3 and melanoma.