Mini-review: androgen receptor phosphorylation in prostate cancer

Androgen receptor (AR) plays an important role in the tumorigenesis and progression of prostate cancer (PCa), and is the primary therapeutic target for PCa treatment. AR activity can be regulated via phosphorylation at multiple phosphorylation sites within the protein. Modifications by phosphorylation alter AR function, including its cellular localization, stability and transcriptional activity, ultimately leading to changes in cancer cell biology and disease progression. Here we present a brief overview of AR phosphorylation sites in PCa, focusing on functional roles of phospho-AR (p-AR) species, relevance in PCa disease progression, and potential as biomarkers and/or therapeutic targets through the use of kinase inhibitors. Additionally, recent evidence has shown the important role of AR activity in the cancer associated stroma on PCa growth and progression. The phosphorylation status of epithelial and stromal AR may be distinct; however, the current data available on stromal AR phosphorylation is limited. Further research will determine global view on the synergistic effects of phosphorylation across multiple AR sites in both epithelial and stromal cells and validate whether together they can be used as prognostic markers and/or effective therapeutic targets for PCa.