Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications

In last years several improvements have been made in the management of prostate cancer (PCa). Androgen receptor (AR) is considered the main driver in PCa growth and progression and most drugs are directed against AR pathway. Once PCa spreads outside the prostate, androgen deprivation therapy (ADT) represents the cornerstone of treatment in hormone-sensitive prostate cancer (HSPC). Unfortunately, the response is only transient and most patients eventually develop castration-resistant prostate cancer (CRPC). Most resistance mechanisms depend on maintenance of AR signalling in castration environment. Recent discoveries of multiple growth-promoting and survival pathways in PCa suggest the importance of alternative mechanisms involved in disease progression, such as DNA damage response pathway, PTEN/PI3K/AKT/mTOR pathway, cell cycle pathway, WNT pathway, TMPRSS2/ETS fusion, neuroendocrine pattern and immune system response. In this review, we discuss the interplay between AR signaling and other molecular pathways involved in PCa pathogenesis and their therapeutic implication in advanced disease.