Interactions Between The Androgen Receptor And Other Signaling Pathways Implicated In Prostate Cancer Growth And Development

Prostate cancer is the second most prevalent type of cancer diagnosed in men in the western world and the leading cause of cancer mortality in older men. Since early-stage development of prostate cancer depends on androgens for growth and survival, androgen deprivation by surgical or chemical castration has been used as the main therapeutic intervention in the treatment of the disease. Despite initial responsiveness to androgen ablation therapy, tumor cells invariably progress to an androgen-independent and antiandrogen resistance that is untreatable, ultimately leading to mortality. It is well established that androgen receptor mediated signaling is critical not only in normal prostate functioning but also in the development and progression of prostate cancer. Given its pivotal role in prostate cancer progression, it is important to delineate its interaction with other signaling pathways that may contribute to prostate cancer growth and development. This is particularly necessary since the signaling mechanisms involved in the transition from normal to androgen-dependent and then to androgen-independent prostate cancer are poorly understood. It has become increasingly evident that crosstalk exists between the androgen receptor and other signaling pathways. This suggests the existence of a coordinated mechanism where there is a converging point for generated signals, thereby driving prostate cancer growth and aggressiveness, downstream. This review therefore focuses on the role that the androgen receptor plays in the major signaling pathways implicated in prostate cancer development and progression.