Esophageal adenocarcinoma in "mice and men": back to basics!

Adenocarcinoma related to Barrett's esophagus (BE) is increasing in the West faster than any other cancer. There are many potential chemopreventive agents as well as predictive biomarkers of cancer progression, but what is required is a robust high-throughput model in which to test hypotheses preclinically. The pathophysiology of metaplasia and cancer has been studied in 10 animal species. Though they have considerable genetic divergence, anatomical dissimilarity, and experimental flaws, they have provided some data to test in the clinic, especially relating to activation of common genetic pathways, role of hypergastrinemia, and duodenogastric reflux in cancer progression. In this regard, the human postesophagectomy model, which has a 30% recurrence of BE within 3 yr and a 5% recurrence of adenocarcinoma over 10 yr, is now being utilized to understand how human metaplasia occurs. Furthermore, improved clinical trial designs mean that more sophisticated questions can be addressed in man.