Treatment options in androgen-independent prostate cancer

Metastatic prostate cancer is a leading cause of cancer-related death in me n. Although most patients will respond to androgen ablation as initial syst emic therapy, nearly all patients will develop androgen-independent prostat e cancer (AI CaP) and will succumb to the disease. Advances in molecular bi ology have demonstrated mutations in and persistent expression of the human androgen receptor in metastatic disease. Furthermore, recent evidence indi cates that an apoptotic block through p53 mutations or bcl-2 overexpression may have a potential role in the poor responses seen with standard chemoth erapy. Presently, the six general treatment options available for AI CaP ar e best supportive care, radiation therapy, radioisotopes, second-line hormo nal therapy, chemotherapy (single agent or combination), and investigationa l therapies such as monoclonal antibodies, cyclin-dependent kinase inhibito rs, matrix metalloproteinase inhibitors, and antiangiogenesis agents, among others. None of these modalities have produced durable remissions, althoug h some have demonstrated palliative benefit. The next generation of clinica l trials should not consist of futile hormonal manipulations or repetitive chemotherapy. Therapeutic strategies aimed at circumventing molecular block s to cell death or targeting unique cancer molecules and genes will be more likely to improve quality of life and longevity Furthermore, the aggressiv e use of palliative care will ensure effective caring for patients and the healing of families in the absence of cure.