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Development of drugs against hormone‐refractory prostate cancer

The development of novel drugs for prostate cancer refractory to androgen deprivation therapy has been of great interest due to the lack of effective treatment modalities that can prolong the survival of such patients. The recent introduction of docetaxel‐based combination chemotherapy has been a breakthrough with a modest, but significant, survival benefit. However, the improved survival period measured in months is far from ideal considering the non‐negligible adverse events associated with docetaxel. Thus, numerous preclinical and clinical studies have been conducted to explore more favorable approaches to hormone‐refractory prostate cancer. The novel agents under investigation include new chemotherapeutic drugs, drugs targeting signal transduction pathways, apoptosis modulators, drugs targeting the tumor microenvironment, molecular chaperone inhibitors, and dietary ingredients. Unfortunately, none of these agents have shown superior single‐agent activity relative to docetaxel‐based therapy to date. Therefore, developing the most effective combination therapies of new agents and docetaxel‐based chemotherapy seems to be a reasonable approach until novel agents that can overcome the drug resistance of hormone‐refractory prostate cancer cells emerge. Drug Dev Res 69:431–450, 2008. © 2008 Wiley‐Liss, Inc.