AR and neoplasm: We hypothesized that similar to metabolic mechanisms that elicit DHT synthesis, which in turn stimulate AR in CRPC (Chang et al., 2013; Knudsen and Penning, 2010; Sharifi, 2013), a role for GR in enzalutamide resistance would be accompanied by a tumor metabolic switch that provides sustained tissue cortisol concentrations that enable GR activation.