Signaling for the caspases: their role in prostate cell apoptosis

PURPOSE: The caspases are an evolutionary conserved family of cell death proteases. Their activation during apoptosis is an important underlying theme in prostate cancer therapy. We summarize the signaling pathways leading to the recruitment of the caspases and address the importance of recent therapeutic strategies aimed at specifically targeting these proteases in relation to prostate cancer. MATERIALS AND METHODS: We present a background introduction into the role of the caspases in apoptosis and how failure to signal effectively their activation may contribute to prostate cancer progression. Key studies aimed at specifically targeting the caspases as cancer therapy are discussed. RESULTS: Prostate carcinogenesis and apoptosis are related. The deregulation of apoptosis contributes to tumor initiation, metastasis and progression to the androgen insensitive state. Conversely the effectiveness of therapy often depends on its ability to induce apoptosis in prostate cancer cells. Identifying abnormalities in the apoptotic signaling pathway has greatly contributed to understanding the biology of prostate cancer. Elucidating caspase regulation has contributed to the design of novel therapies for prostate cancer. CONCLUSIONS: We summarize the physiological and pathological pathways leading to caspase activation in the prostate and describe novel approaches that target these proteases.