Hormonal manipulation in androgen signaling: a narrative review on using novel androgen therapy agents to optimize clinical outcomes and minimize side effects for prostate cancer patients

Prostate cancer is a significant public health burden and one of the most common cancers globally and in the United States. The current cornerstone of prostate cancer systemic treatment involves the suppression of androgen receptor (AR) signaling, either by reducing the body’s testosterone production or inhibiting its binding to AR and its subsequent gene regulatory network driving carcinogenesis. This signaling pathway plays a central role in both hormone sensitive and castration resistant prostate cancer (CRPC), as evidenced by survival benefit when AR-targeted therapies are applied in the setting of CRPC. With the development of increasingly potent central and peripherally acting androgen targeting agents physicians treating prostate cancer can expect to treat their patients for a longer duration with a larger selection of effective agents. In this setting clinicians are now faced with questions of how to best tailor treatments for the prostate cancer patient to not only maximize overall survival but also optimize the quality of life and mitigate toxicity. In this manuscript we discuss the newer hormone therapy agents for prostate cancer and highlight what they indicate about optimizing medical castration, and the potential value of peripheral blockade.