Management of Metastatic Castration-resistant Prostate Cancer

Abstract

The management of men with metastatic castration-resistant prostate cancer (CRPC) has taken several leaps forwards in the last two years, with the demonstration of improved overall survival with three novel agents (sipuleucel-T, cabazitaxel and abiraterone acetate) and a significant delay in skeletal-related events observed with denosumab. The pipeline of systemic therapies in prostate cancer remains strong, as multiple agents with a diverse array of mechanisms of action are demonstrating preliminary signs of clinical benefit, leading to more definitive Phase III confirmatory trials. In this review, we will discuss the evolving landscape of treatment options for men with CRPC, with a particular focus on currently approved and emerging treatment options for these patients. Knowledge of these evolving standards will help to optimise delivery of care and long-term outcomes in men with advanced CRPC. KeywordsCastration-resistant prostate cancer, novel therapies, drug development, sipuleucel-T, cabazitaxel, abiraterone, denosumab, orteronel, MDV3100, ipilimumabDisclosure: Emmanuel S Antonarakis has served as an advisor/consultant for Sanofi-Aventis. While much of the recent focus on prostate cancer relates to the over-diagnosis and over-treatment of this disease, each year almost 100,000 men in Europe and more than 30,000 men in the US still die of advanced prostate cancer, making it the second most common cause of cancer-related deaths.1 Androgen deprivation therapy is the most effective systemic treatment for recurrent prostate cancer; however, the vast majority of these patients will eventually develop resistance to hormonal approaches (see Table 2).

Molecular characterization of a novel androgen receptor transgene responsive to MicroRNA mediated post-transcriptional control exerted via 3′-untranslated region

“…Abiraterone acetate impedes testosterone production by targeting CYP17A and Enzalutamide is an AR‐antagonist . However, PCa patients develop resistance to these drugs due to accumulation of AR mutations as a result of sequential therapies . In most cases of CRPC, AR protein level is increased in the prostate tissue which drives the disease progressively to metastatic CRPC .…”