Nuclear receptor coregulators: Promising therapeutic targets for the treatment of prostate cancer

The concept that androgens exert control over the prostate and prostate disease dates back to the eighteenth century, when the first observations of seasonal variations in the size of the prostate gland were observed in animals. Since then, a direct link between testis-derived androgens and prostate growth was established, leading to the seminal study of Charles Huggins who demonstrated that surgical or medical castration is able to inhibit the growth of metastatic and advanced prostate cancer (CaP). Today, more than six decades after Huggins' original groundbreaking report, so-called androgen deprivation therapies are still the preferred treatment option for CaP patients who do not benefit from surgery or radiation therapy. While such treatment regimes initially result in a clinical favorable response and an overall decrease in tumor burden in a majority of patients, disease regression is not complete, and androgen deprivation is therefore not curative. Recent findings of physiologically relevant tissue levels of androgens in castration-recurrent prostate cancer (CRPC) have led to a paradigm shift that CaP, which recurs following androgen deprivation therapy, is not androgen-independent and has rekindled research into alternative means of blocking androgen action as a therapeutic option during prostate cancer progression. Here, we explore the possibility of targeting coregulator proteins, which are critical determinants for androgenic responses, as an indirect means of blocking androgen action in CaP cells.