Narrative review of challenges in the management of advanced neuroendocrine prostate cancer

With wide availability of potent androgen receptor targeted agents (ARTAs), the incidence of treatment-related neuroendocrine prostate cancer (t-NEPC) has been dramatically increasing. However, there is no standard effective treatment for this disease state. Recent advances in genomic and molecular medicine have identified some critical features of NEPC that would help in understanding the biology of the disease. Furthermore, invaluable pre-clinical in vivo and in vitro research models that represent NEPC have been developed. These advances in research have revealed a large heterogeneity of t-NEPC with varying degree of androgen receptor (AR), neuroendocrine (NE) marker, and cell cycle associated gene expressions, which may have clinical implication in terms of prognosis and treatment selection. Based on these studies, some potential drug targets have been identified, and early clinical trials are ongoing. In the future, more precise disease classification and biomarker-driven selection of patients will be critical for optimization of treatment for patients with NEPC. In the present review, we describe up-to-date findings of recent research on this topic and introduce ongoing therapeutic developments that are expected to lead to novel treatment strategies for NEPC in the future.