Together, these results indicate fundamental differences in sensitivities to combined AR/AKT inhibition with apalutamide and the pan-AKT inhibitor GSK690693, particularly in the context of Pten-deficient castration-sensitive and insensitive prostate cancer, as well as early-stage and late-stage cancer and/or Trp53 status. This evidence concerns the gene TP53 and Familial prostate cancer.