Molecular markers and determinants of prostate cancer metastasis

Although intensely studied, the molecular and biochemical determinants of p rostate cancer development and progression remain ill-defined. Moreover, cu rrent markers and methodologies cannot distinguish between a tumor that wil l remain indolent and not impinge on patient survival, versus a tumor with aggressive traits culminating in metastatic spread and death. Once prostate cancer is confirmed the most significant threat to a patient's survival an d quality of life involves tumor metastasis. Radical surgery notwithstandin g, prostate cancer accounts for 10% of all cancer-related deaths primarily arising through development of metastasis. Metastasis markers demonstrating an acceptable level of reliability are an obvious necessity if disproporti onate and costly treatment is to be avoided and a reasonably accurate deter mination of clinical prognosis and measure of successful response to treatm ent is to be made. Therapeutic strategies that specifically inhibit metasta tic spread are not presently possible and may not become available in the i mmediate future. This is because, while localized tumorigenesis has been re latively amenable to detection, analysis and treatment, metastasis remains a relatively undefined, complex and underexplored area of prostate cancer r esearch. New findings in the field such subclasses of genes called metastas is suppressors and cancer progression suppressors, have opened up exciting avenues of investigation. We review current methodological approaches, mode l experimental systems and genes presently known or having potential involv ement in human prostate cancer metastasis. (C) 2001 Wiley-Liss, Inc.