Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and the fifth leading cause of cancer death in men worldwide. At the initial stages, Pca cells are dependent upon androgens for their growth and hence effectively combated by androgen deprivation therapy (ADT) until PCa recurs during hormonal therapy and became hormone refractory or castration-resistant prostate cancer (CRPC). The role of AR signaling in PCa development and progression has been well established. Transition from hormone responsive to CRPC might be driven by a wide range of genetic and cellular events leading to distinct progression pathways either dependent or independent of the AR activity. Thus, the role of other signaling cascades (i.e. STAT3 pathways) in PCa development and progression should be investigated. In CRPC a metabolic reprogramming is induced and there are substantial evidences implicating environmental factors, as well as chemical and pollutant agents, in metabolism shift, in chemo-resistance and in hormone refractory of PCa. Understanding the mechanisms of resistance that cause hormone-naive prostate cancer to progress to castration-resistance is the key to developing future therapies.
