While the downregulation of some growth related genes such as BIRC5 and CDK1 by enzalutamide (Supplementary Figures S1 and S2) may account for enzalutamide-induced growth inhibition of prostate cancer cells (9,16), the upregulation of cancer-promoting genes such as NR3C1 (23,43), SLC7A11 (24–26) and LAMP3 (44) by enzalutamide-liganded AR (Figure 1, Supplementary Figures S1, S3 and S10) suggests that these pathways may contribute to the emergence of resistance and that an opportunity exists to improve the therapeutic efficacy of enzalutamide by blocking these effects simultaneously. Here, AR is linked to prostate carcinoma.