In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR) targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory phosphatase and tensin homolog (PTEN) activates phosphoinositide 3-kinase (PI3K)/AKT signaling and contributes to resistance to androgen-deprivation therapy and poor outcomes.