Prostate cancer prevention strategies using antiproliferative or differentiating agents

Differentiation or antiprolifeuative therapies have been most effective in the treatment of promyelocytic leukemia and are being investigated for the treatment of solid tumors including prostate cancer (PCa). Research suggest s that these agents may induce terminal differentiation (arrest in C,), ind uce differentiation to a mature cell with cellular functions and a growth p attern similar to nonmalignant cells, or trigger apoptosis. This review foc uses on classes of agents under laboratory and clinical evaluation as antip rolifeuative or differentiating agents: polyamine inhibitors, vitamin D and its analogs, metabolites of vitamin A, the short-chain fatty acid, phenylb utyrate, and nonsteroidal anti-inflammatory agents. Because differentiation therapies offer a reduced toxicity profile and have potential for preventi ng or slowing cancer progression, they map offer an alternative to chemothe rapy for men with advanced PCa, or may be useful as low-toxicity agents giv en chronically for chemoprevention in men at high risk for PCa. Clinical tr ials are needed to define the role of these agents in primary and secondary prevention. (C) 2001, Elsevier Science Inc.