Drivers of neuroendocrine prostate cancer

Prostate cancer (PCa) is the most common malignancy in men and remains a leading cause of cancer death in males worldwide (1). The mainstay for patients with advanced and metastatic PCa, including castration-resistant disease, is hormonal therapy that targets the androgen receptor (AR) (androgen deprivation therapy) (2). Recently potent AR-targeted therapies were approved for the treatment of men with castration-resistant prostate cancer (CRPC), as de case of enzalutamide and abiraterone (3,4). While the use of these agents improves the survival of individuals with CRPC, most of them eventually develop resistance to therapy with a lethal outcome (5). This phenomenon may reflect an epithelial plasticity that enables tumor adaptation in response to AR-target therapies, which is not fully understood.