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
Keywords: Androgens, androgen receptors (AR), androgen synthesis inhibitors, AR antagonists, cytotoxic GnRH-based hybrid
compounds, gonadotropin-releasing hormone (GnRH), GnRH analogs, GnRH receptors (GnRH-R).
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