Importantly, preclinical analyses using in vivo mouse models of RCC revealed that targeting of this newly identified ERβ/TGF‐β1/SMAD3 pathway with either the FDA‐approved anti‐estrogen ICI182,780 (Faslodex) or a selective ERβ antagonist 4‐[2‐phenyl‐5,7 bis(trifluoromethyl)pyrazolo[1,5‐a]pyrimidin‐3‐yl]phenol can significantly reduce RCC tumor growth and invasion, which may be suitable as the basis for novel therapies to more effectively suppress metastatic RCC. The gene discussed is SMAD3; the disease is neoplasm.