Neuroendocrine differentiation in prostate cancer: a sheep in wolf's clothing?

Neuroendocrine differentiation of the prostate is often associated with a dismal prognosis. Whilst it is relatively rare compared with other forms of prostate cancer, it nevertheless remains difficult to treat these cancers effectively and to maintain a durable response. Research aimed at understanding the complexity of neuroendocrine differentiation of the prostate has been conducted for some time. The cells involved in this process secrete a variety of factors that can influence growth patterns and regulatory pathways. Many of these factors can be monitored serologically, but the relationship between the biology of the tumor and clinical response is often discordant. This review outlines the difficulties in treating this disease, both at the time of diagnosis and in the metastatic setting, and focuses on an area of research that remains challenging to both the researcher and clinician.