Cancer chemoprevention, as first defined by Sporn in 1976 , uses natural, synthetic, or biological chemical agents to reverse, suppress, or prevent carcinogenic progression. It is based on the concepts of mul-tifocal field carcinogenesis and multistep carcino-genesis. In field carcinogenesis, diffuse epithelial injury in tissues such as the aerodigestive tract, results from generalised carcinogen exposure throughout the field and clonal proliferation of mutated cells. Genetic changes exist throughout the field and increase the likelihood that one or more premalignant and malignant lesions may develop within that field. Multistep carcinogenesis describes a stepwise accumulation of alterations, both geno-typic and phenotypic. Arresting one or several of the steps may impede or delay the development of cancer. This has been described particularly well in studies involving precancerous and cancerous lesions of the head and neck, which focus on oral premalignant lesions (leukoplakia and erythroplakia) and their associated increased risk of progression to cancer. In addition to histologic assessment, intermediate markers of response are needed to assess the validity of these therapies in a timely and cost-efficient manner.
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