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Hypoxia-Inducible Factor 1 as a Possible Target for Cancer Chemoprevention

Department of Pharmacology, Faculty of Pharmacy, University of Seville, Sevilla, Spain

Requests for reprints: Miguel López-Lázaro, Department of Pharmacology, Faculty of Pharmacy, University of Seville, C/ Prof. Garcia Gonzalez, 41011, Sevilla, Spain. Phone: 34-954-55-61-24; Fax: 34-954-23-37-65. E-mail: mlopezlazaro{at}us.es

Despite the intense cancer research carried out in the last 30 years, cancer therapy has not managed to decrease cancer mortality. We need new strategies to control a disease that kills over six million people worldwide every year. It is accepted that cancer chemoprevention (the use of chemicals to prevent, stop, or reverse the process of carcinogenesis) is an essential approach to controlling cancer; yet, the clinical usefulness of this strategy is very limited. Successful implementation of cancer chemoprevention depends on a mechanistic understanding of the carcinogenesis process. Our knowledge about this process is still limited and may therefore be preventing cancer chemoprevention from becoming a widely used anticancer tool. This report discusses recent evidence that suggests that the activation of the hypoxia-inducible factor 1 (HIF-1) is a key event in carcinogenesis and may therefore represent a key target for cancer chemoprevention. Based on an understanding of the mechanisms responsible for HIF-1 activation, possible general strategies for targeting HIF-1 are proposed. Successful implementation of these strategies might turn the great promise of cancer chemoprevention into a fundamental tool for reducing the burden of this disease. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2332–5)

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