Based on that (1) elevated levels of TGF-β1 in enzalutamide-treated prostate cancers occurred concurrently with activation of STAT3 and enhanced EMT; and (2) metformin is capable of downregulating TGF-β1, inhibiting STAT3 activation and more importantly the enzalutamide-induced EMT, we speculate that one of the mechanisms in metformin-mediated reversal of enzalutamide resistance is by targeting EMT via TGF-β1/STAT3 axis. This evidence concerns the gene STAT3 and prostate cancer.