Squamous cell carcinoma (SCC) of the human esophagus has a multifactorial etiology involving several environmental and/or genetic factors. Current modalities of
therapy for this disease offer poor survival and cure rates. Although a number of approaches could be undertaken to reduce the occurrence of esophageal SCC, including changes in lifestyle and improved nutrition, such approaches are not easily implemented.
Chemoprevention offers a viable alternative that is likely to be effective against this disease. Clinical investigations in areas of high incidence of esophageal SCC have shown that primary
chemoprevention of this disease is feasible, if potent inhibitors are identified. Studies in the Fischer 344 rat model of
nitrosamine-induced
tumorigenesis have proven valuable in understanding the biology of esophageal SCCs and help identify
surrogate end-point biomarkers and putative agents that can be useful in human
chemoprevention studies. Several compounds that inhibit
tumor initiation by suspected human esophageal
carcinogens have been identified using this model. These include
diallyl sulfide,
isothiocyanates and several polyphenolic compounds. Novel
biomarkers, including nuclear/nucleolar morphometry using computer-assisted image analysis of preneoplastic lesions, have been developed to measure efficacy of chemopreventive agents against esophageal SCC. The identification of single agents that inhibit the progression of dysplastic lesions, however, has proven difficult. Results from a food-based approach suggest that the use of freeze-dried berry preparations can affect both initiation and promotion/progression of esophageal SCC in an animal model. These observations provide valuable information for future studies on
chemoprevention of
cancers of the esophagus in a clinical setting. Given the complex etiology of esophageal SCC, it is felt that the most effective
chemoprevention strategies would include agents that reduce mutational events associated with
carcinogen exposure in combination with agents that inhibit the progression of intraepithelial dysplasia to invasive
cancer.