Progress in chemoprevention of gastrointestinal cancers.

Carcinogenesis is a complex and multistep process. Numerous inhibitors (either naturally occurring or synthetic) have been identified that can interfere with various phases of carcinogenesis, including the endogenous formation of carcinogens, the activation or detoxification of carcinogens, or events in tumor promotion. Many of these compounds have survived a complex screening program and are currently in or ready for clinical application. In gastrointestinal malignancies, colon neoplasia has been a popular target for chemoprevention. The identification of preneoplastic events in colon mucosa or in the progression of malignancy from adenomas to adenocarcinomas has permitted the study of numerous compounds such as calcium salts, difluoromethylornithine, and prostaglandin synthesis inhibitors on intermediate biomarkers or on the development of recurrent adenomas or cancers. A variety of other compounds with general efficacy in other tumor models have also been shown to be effective inhibitors of tumorigenesis in preclinical models of esophageal, gastric, pancreatic, and hepatic carcinogenesis. This review provides an overview of carcinogenesis and principles of chemoprevention and highlights certain developments in the past year that exemplify the experience and progress in this area.