ABSTRACT
Prostate cancer is the second leading cause of cancer death in American men accounting for over 180,000 new cases and approximately 28,000 deaths annually. Since, aberrant apoptotic pathways contribute to initiation and progression of neoplasia, including prostate cancer, pro-apoptotic agents are attractive for treatment of advanced prostate cancer. Th erefore, inhibiting anti-apoptotic molecules or potentiating pro-apoptotic molecules can serve as excellent treatment strategies for treatment of prostate cancer. Alterations in many apoptotic related genes including the Bcl-2 family proteins, NF-κB, p53, PTEN/P13K/AKT, caspase and inhibitors of apoptosis proteins (IAP) have been implicated in prostate progression. Moreover, apoptosis related genes also play a signifi cant role on radioresistant and hormone-independent forms of prostate cancer. A promising agent, TRAIL, induces apoptosis in cancer cells, but spares normal cells, therefore, it is an ideal cancer therapeutic agent with minimal cytotoxicity. However, some cancer cells develop resistance to pro-apoptotic agents. Th erefore, overcoming resistant
cancer cells and identifying patients who may benefi t the most from pro-apoptotic therapies is important in treatment of patients with advanced prostate cancer. Defi ning the apoptotic mediated signal transduction pathways and the intricate molecular interactions will help guide us in developing drugs with less toxicity for appropriately selected patients with prostate cancer and other malignancies.
