Prostate cancer is the second leading cause of cancer-related death in men in most western countries [1]. Recently, several drugs with different mechanisms of action have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). In addition, next-generation antiandrogens such as orteronel, ARN-509 and galeterone are under investigation in several trials [1]. Understanding tumor biology will become increasingly important for therapeutic decisions in the near future. Considering all these data, we deem that targeting the AR pathway, along with the PI3K/Akt/mTOR signaling in acquired PTEN loss metastatic CRPC, that is resistant to novel antiandrogenic therapies, maybe an interesting approach that needs to be tested in clinical studies. There are several potential predictive biomarkers which may help in the identification and selection of patients suitable for this novel therapeutical approach.
