Altogether, these results indicate that metformin can reverse enzalutamide resistance by counteracting enzalutamide-mediated STAT3 activation, subsequent upregulation of TGF-β1 and ultimate prostate cancer invasion and metastasis (Figure 6), suggesting that combination of metformin and enzalutamide could be more efficient in treating castration-resistant prostate cancer. Here, STAT3 is linked to Familial prostate cancer.