Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway has been strongly linked with prostate cancer progression and metastatic potential.1 Loss of the inhibitory phosphatase, PTEN, leading to hyperactivation of PI3K/AKT/mTOR oncogenic signaling, occurs in 40-50% of metastatic castration-resistant prostate cancer.1,2 Not surprising is the fact that PTEN loss in patients with metastatic castration-resistant prostate cancer is associated with a worse prognosis and less benefit from androgen receptor (AR) blockade.3 Likewise, PTEN loss and subsequent Akt activation confer radiation4 and chemotherapy5, 6 resistance.