In the current issue of Frontiers in Oncology – Cancer Endocrinology Section, Yin et al. report that the aldo-keto reductase family 1 member C3 (AKR1C3) inhibitor SN33638 was able to reduce testosterone production, PSA expression, and cell proliferation only in some castration-resistant prostate cancer (CRPC) cells, overexpressing the enzyme, but not the majority of a panel of prostate and breast cell lines investigated, and revealing a novel caveat in developing AKR1C3 inhibitors for cancer therapy. The gene discussed is AKR1C3; the disease is cancer.