AKR1C3 and Familial prostate cancer: Liu et al. demonstrated that AKR1C3, a critical enzyme in the biological pathways that lead to the production of testosterone and DHT from weak androgens (androstenedione and 5 α-androstenedione), is upregulated in enzalutamide-resistance prostate cancer cells and that indomethacin, an inhibitor of AKR1C3 activity, could overcome this resistance, reducing cell proliferation [26].