Biomarkers and molecular imaging in gastrointestinal cancers

The best means to improve gastrointestinal cancer survival is screening and treatment of early lesions. In esophageal adenocarcinoma, it is believed that low-grade dysplasia and perhaps even high-risk Barrett's esophagus represent the most attractive targets for achieving a cure. An issue with Barrett's esophagus is that endoscopy alone cannot distinguish Barrett's esophagus from columnar-lined epithelium or from areas of low-grade dysplasia. Much effort, therefore, has been devoted to discover molecular biomarkers of high-risk states and to develop imaging tools for detecting these biomarkers in a manner that could assist real-time in vivo targeting of sites for biopsy. The strategy we have used is to generate stem cell clones from Barrett's esophagus biopsy specimens and to compare their gene expression profiles with patient-matched stem cell clones of the esophageal squamous epithelia and gastric cardia. It is anticipated that by mining the expression data sets of these Barrett's stem cell clones, we will be able to identify unique cell surface markers of the Barrett's stem cells against which cytotoxic antibodies or aptamers can be developed and used to aid the endoscopist in identifying regions of atypia for biopsy, perform a real-time diagnosis, stratify patients during the examination, and, ultimately, direct therapy in a preemptive manner.