Mechanisms of prostate cancer progression to androgen independence

Prostate cancer is a major health problem in the United States and worldwide. In 2007, more than 27,000 men were estimated to have died from prostate cancer in the United States alone. Although important advances have been made in the diagnosis and treatment of prostate cancer, therapies focused on the removal or inhibition of androgen action remain the most important components of therapy for individuals with metastatic disease. Despite the application of such modalities, the vast majority of patients with metastatic disease progress with a median survival of less than 2 years. A number of different mechanisms have been identified that may potentially contribute to the progression of prostate cancer. These insights suggest that signaling via the androgen receptor (AR) – either via alternate signaling pathways impinging on the AR or through the in situ formation of androgens within progressive tumors – is an important contributor to such progressive disease. It is anticipated that such mechanistic insights will lead to the development of useful new therapies in the future.