The present invention encompasses the recognition that reproducible and detectable changes in the level and or activity of SGK1 are associated with incidence and/or risk of Castration Resistant Prostate Cancer (CRPC) and/or doubly resistant prostate cancer, specifically in individuals having prostate cancer and on antiandrogen therapy, and provides for the use of SGK1 inhibitors to treat and/or reduce risk of CRPC and/or doubly resistant prostate cancer. In some embodiments, SGK1 inhibitors also have Glucocorticoid Receptor (GR) and/or Androgen Receptor (AR) inhibitory activity or are administered in conjunction with GR and/or AR inhibitors.