Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all
cancer-related mortality worldwide. This
malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since
esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates.
Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary
chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit
tumor initiation by esophageal
carcinogens have been identified using this model. These include several
isothiocyanates,
diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal
carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into
tumors. These agents include inhibitors of
inducible nitric oxide synthase (iNOS),
cyclooxygenase-2 (COX-2),
vascular endothelial growth factor (
VEGF) and c-Jun [a component of
activator protein-1 (AP-1)]. Using a food-based approach to
cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.