Targeting Apoptosis in Prostate Cancer

Prostate cancer was diagnosed in more than 180,000 men in the year 2000.2 Despite initial local therapy with surgery or radiation, many patients experience recurrence with advanced disease. Androgen ablation therapy produces only temporary responses because of the development of androgen independence.42, 43 After failure of androgen ablation, resistance to chemotherapy develops quickly in patients treated with combinations of cytotoxic agents.16, 41, 43, 51 Molecular changes that occur during the progression of prostate cancer affect programmed cell death pathways and are associated with resistance to chemotherapy. These changes include mutations in p53 and overexpression of bcl-2.1, 51, 53, 63, 72, 77 Approaches that alter the expression or function of these and related proteins may improve therapeutic results.34, 35, 27, 23, 68, 83 This article reviews current efforts to modulate apoptotic pathways and define new targets that could be important in the treatment of prostate cancer.