Esophageal cancer is associated with GERD (gastrointestinal reflux disease), obesity, alcohol, and tobacco abuse. But the long march toward malignancy starts 10 to 20 years earlier when the cells, genes, and signaling pathways in the foregut begin a nefarious cooperative dance.
Jianwen Que, a junior faculty in the URMC Department of Biomedical Genetics, has been studying the basic biology of these pre-cancerous lesions. Inflammation is a major trigger. The hope is that someday scientists will have enough evidence to support the use of anti-inflammatory drugs, perhaps paired with acid reflux medications, to prevent this devastating cancer. (Survival rates can be as low as 5 to 20 percent if the cancer has spread by the time it’s diagnosed.)
In a paper published recently in Cell Stem Cell, Que and his team answered some important fundamental questions. First, they discovered that basal stem/progenitor cells are the cells of origin for this cancer. They also showed in mice for the first time, how squamous cell lesions arise from the interplay between genes in the esophagus. The inflammatory environment activates a transcription factor called STAT3, which then cooperates with another gene known as SOX2, which is specifically expressed in the basal stem cells of the esophagus. Together SOX2 and STAT3 seem to be required for promoting esophageal tumor growth.
Timothy C. Wang, an oncologist and researcher at Columbia University, who wrote an accompanying preview article in Cell Stem Cell, applauded the Wilmot team for piecing together the critical steps in the malignant transformation process.
Now scientists might have a better opportunity to design an intervention. To see the abstract or full study in Cell Stem Cell: http://www.cell.com/cell-stem-cell/abstract/S1934-5909(13)00010-6