Endocr Relat Cancer. 2015 May 1. pii: ERC-15-0137. [Epub ahead of print]

Regulation of tumor cell plasticity by the androgen receptor in prostate cancer.

Bishop JL¹, Davies AH², Ketola K³, Zoubeidi A⁴.

Abstract

Prostate cancer has become the most common form of cancer in men in the developed world and ranks second as the cause of cancer-related deaths. Men that succumb to PCa have disease that is resistant to hormonal therapies that suppress androgen receptor (AR) signaling, which plays a central role in tumor development and progression. While the AR continues to be a clinically relevant therapeutic target in in PCa, selection pressures imposed by androgen deprivation therapies promote the emergence of heterogeneous cell populations within tumors that dictate the severity of disease. This cellular plasticity, induced by androgen deprivation, is the focus of this review. More specifically, we will address the emergence of cancer stem-like cells, epithelial-to-mesenchymal or myeloid plasticity, and neuroendocrine transdifferentiation and evidence supporting how each is regulated by the AR. Importantly, as all of these cell phenotypes are associated with aggressive PCa, we examine novel therapeutic approaches to targeting therapy induced cellular plasticity as a way to prevent PCa progression.