Researchers at Columbia University Medical Center (CUMC) have identified the critical early cellular and molecular events that give rise to a type of esophageal cancer called esophageal adenocarcinoma, the fastest-rising solid tumor in the United States. The findings, published online today in Cancer Cell, challenge conventional wisdom regarding the origin and development of this deadly cancer and its precursor lesion, Barrett's esophagus, and highlight possible targets for new clinical therapies.
Lacking a good animal model of esophageal adenocarcinoma (EAC), researchers have been hard pressed to explain exactly where and how this cancer arises. What is known is that EAC is usually triggered by gastroesophageal reflux disease (GERD), in which bile acid and other stomach contents leak backwards from the stomach to the esophagus, the muscular tube that moves food from the mouth to the stomach. Over time, acid reflux can irritate and inflame the esophagus, leading to Barrett's esophagus, an asymptomatic precancerous condition in which the tissue lining the esophagus is replaced by tissue similar to the lining of the intestine. A small number of people with Barrett's esophagus eventually go on to develop EAC.
Using a new genetically engineered mouse model of esophagitis, the CUMC researchers have clarified critical cellular and molecular changes that occur during the development of Barrett's esophagus and EAC. In human patients, acid reflux often leads to overexpression of a molecule called interleukin-1 beta, an important mediator of the inflammatory response, reported study leader Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at CUMC. Thus, Wang and his colleagues created a transgenic mouse in which interleukin-1 beta was overexpressed in the esophagus.