Continued research in the treatment of castration-resistant prostate cancer (CRPC) has allowed for a clearer understanding of this disease entity and further treatment advances. In a study recently published by Beer et al. [1] in the New England Journal of Medicine, another advance to treatment was demonstrated for the androgen receptor (AR) signaling inhibitor, enzalutamide, in patients with chemotherapy-naïve metastatic CRPC. Although a large majority of patients responded favorably to enzalutamide in the prechemotherapy setting, a small but significant proportion of patients demonstrated no meaningful benefit to this agent. This highlights an important concept in the understanding of this disease: inherent and acquired resistance to AR-targeting therapies.

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