The invention provides compositions and methods for treating and preventing cancer. The invention relates to compositions and methods for treating subjects having a cancer associated with overexpression of estrogen receptors, especially in males. The invention comprises inhibitors of ERβ, inhibitors of TGFβ-1, inhibitors of SMAD, or inhibitors of HIF, or a combination thereof. In one embodiment, the invention provides a method of treating renal cancer, including renal cell carcinoma.