The importance of cellular androgenic hormonal mechanisms in treatment and progression of prostate cancer

Since the seminal work of Charles Huggins, androgen deprivation therapy (ADT) has been the treatment of choice of advanced PCa. The dramatic effect of ADT results from the dependence of prostate cancer cell on androgen for growth and normal function. Most prostate cancer however are able to growth in absence of serum testosterone, a phenomenon coined castration-resistance. This largely explains why, despite initial response of great magnitude, ADT is essentially a palliative treatment with little if no benefit on survival. In the last 10 years, the basic mechanisms explaining resistance to castration have been unveiled leading to the development of new agents able to revert that mechanisms, including recently FDA approved abiraterone and enzalutamide. The most important adaptation progresses are the ability of the cell to produce its own androgens and the mutation and overexpression occurring at the level of the AR. These mechanisms and their practical implications are explained hereafter.