Home > Expanding Androgen- and Androgen Receptor Signaling–Directed Therapies for Castration-Resistant Prostate Cancer Expanding Androgen- and Androgen Receptor Signaling– Directed Therapies for Castration-Resistant Prostate Cancer

Since the discovery by Huggins and Hodges in 1941 that prostate cancer is an androgen-dependent disease,[2] the mainstay of therapy for advanced disease has been androgen deprivation therapy (ADT). Unfortunately, after a variable period of time on ADT, patients eventually progress to the lethal form of prostate cancer in the setting of castrate levels of testosterone. During the past several years, it has become recognized through laboratory models and molecular profiling studies that reactivation of the androgen signaling axis is a key driver of disease progression.[3-7] The findings of a rising prostate-specific antigen (PSA) level; an androgen receptor (AR)-responsive gene; responses to second-line hormonal agents, such as ketoconazole and hydrocortisone, that further lower androgen levels; and reports of response to discontinuation of anti-androgens and other agents that bind to the receptor, all validate the molecular findings.