It is now well established that hormonal pathways are involved in the 
development of prostate cancer towards the castration resistant (CRPC) stage and 
can be effective molecular targets for novel treatment strategies. Most CRPC are 
sensitive to androgens and this can be due to the intratumoral production of 
androgens, androgen receptor (AR) amplification/ mutations and epigenetic 
modifications of AR expression/signaling. Based on these observations, potent 
agents targeting the AR axis were developed: 1) inhibitors of CYP17 (a key 
enzyme in the production of androgens), such as abiraterone and orteronel; 2) AR 
antagonists that bind to AR and impair AR activation, such as enzalutamide and 
ARN-509. Moreover, gonadotropin-releasing hormone receptors (GnRH-R), associated 
with a strong antitumor activity, are expressed in CRPC cells, indicating that 
they might represent an important target for GnRH analog-based therapeutic 
strategies. In addition to GnRH agonists and antagonists (i.e., degarelix), 
cytotoxic GnRH-based bioconjugates, delivering chemotherapeutic drugs to cancer 
cells expressing the GnRH-R, were developed and reported to exert antitumor 
effects on CRPC cells; some of them (i.e., AN-152) have already entered clinical 
trials. This review discusses the most relevant patents and recent observations 
on the anti-cancer efficacy of novel drugs targeting the AR and the GnRH-R 
pathways in CRPC.