AR and prostate cancer: One possible reason for differential responses between treatment regimens is that in some prostate cancers, AR is overactive or mutated independent of abiraterone acetate–targeted upstream events.31,32,33,34 The AR sequence variant may be resistant to upstream therapeutic targeting but still sensitive to enzalutamide.35 Of note, using both enzalutamide and abiraterone acetate together as a first-line combination treatment did not yield significant improvements in OS.36