Targeting androgen receptor signaling: a historical perspective

The first case of prostate cancer was identified by histological examination by J. Adams, a surgeon at The London Hospital, in 1853. In his report, Adams noted that the condition was “a very rare disease”. Now, over 150 years later, with increased life expectancy and screening, prostate cancer has become one of the most common cancers in men. In the United Sates alone, nearly 200,000 men are diagnosed with prostate cancer annually and about 33,000 succumb to their disease. Fifty years ago, men were typically diagnosed with prostate cancer in their seventies with disease that had metastasized to the bone and/or soft tissue. Diagnosis at such an advanced stage was a death sentence, with patients dying within two years. The pioneering work of Charles Huggins in the 1940s found that metastatic prostate cancer responds to androgen deprivation therapy (ADT), ushering in the rational use of hormone therapies that have irrevocably changed the course of prostate cancer disease management. Medical castration was the first effective systemic targeted therapy for any cancer and, to this day, androgen ablation remains the mainstay of prostate cancer therapy.