The role of alpha-blockers in the management of prostate cancer.

Prostate cancer is the second most common cause of cancer death in men in the US. Patients with prostate cancer are initially treated with surgical resection, radiation or antiandrogen therapy. After an initial remission, however, the majority of prostate tumours evolve into a highly aggressive, metastatic androgen-independent state, for which successful therapy has not yet been established. During the past few years, new perspectives have emerged towards the development of preventive and therapeutic approaches for prostate cancer. Quinazoline-based alpha(1)-blockers have been shown to have antitumour efficacy against prostate cancer cells in inducing apoptosis and anoikis via an alpha(1)-adrenoceptor-independent mechanism. Specifically, doxazosin and terazosin can induce apoptosis, inhibit invasion and migration of prostate cancer and endothelial cells, and reduce their adhesion potential to extracellular matrix components, thus enhancing their susceptibility to anoikis. This review discusses recent evidence suggesting the apoptotic efficacy of quinazoline-based alpha(1)-adrenoceptor antagonists, doxazosin and terazosin and speculates on the therapeutic promise of these drugs as novel antitumour agents against prostate cancer. From a drug discovery perspective, separation of the effect of doxazosin on apoptosis in prostate cancer cells from its original pharmacological activity in normal prostate cells, will provide a molecular basis in developing a novel class of apoptosis-inducing agents through lead optimisation.