While anti-androgen therapy, such as enzalutamide and bicalutamide, is a standard of care for advanced prostate cancer patients, these anti-androgens could further induce prostate cancer cell invasion by increasing the expression of TGF-β1, SMAD3, and MMP9 in prostate cancer cell lines both in vitro and in vivo51. Here, SMAD3 is linked to Familial prostate cancer.