The adrenal-permissive HSD3B1 (1245C) allele (so termed because it enables tumors to use adrenal precursors) is a common missense-encoding variant, resulting in a stable form of the enzyme that increases metabolic flux from DHEA to dihydrotestosterone, and is widely validated to confer less benefit from gonadal testosterone suppression alone across many cohorts of men with prostate cancer from around the world (Figure 1A) (5–12). This evidence concerns the gene HSD3B1 and prostate cancer.