Androgen receptor and prostate cancer

Androgens play a key role in the development and progression of prostate cancer, and androgen deprivation therapy (ADT) is the first line treatment for advanced disease. Although ADT is initially successful in controlling prostate cancer, many patients eventually become resistant to therapy and progress to develop lethal castration -resistant prostate cancer (CRPC). Androgens drive prostate cancer cell growth via the androgen receptor (AR), which is a transcription factor essential for prostate cancer cell viability, proliferation and invasion and has important roles in a range of signalling pathways. The progression to CRPC is thought to involve persistence of AR signalling and reprogramming of the AR transcriptional landscape to allow tumour cells to continue to grow despite low levels of circulating androgens. During this time AR activity can be maintained through activating mutations, gene amplification, AR splice variants or signalling crosstalk with other pathways. CRPC is highly aggressive and ultimately lethal, meaning there is an urgent need to understand the mechanisms that drive this form of the disease and to develop new therapeutic targets. This review discusses the role of the AR signalling in some of the many mechanisms and pathways that contribute to the development of prostate cancer and the progression to castrate resistant disease.