Biomarkers and molecular imaging in gastrointestinal cancers.

Wa Xian, The Jackson Laboratory
Frank D. McKeon, The Jackson Laboratory
Khek Yu Ho


The best means to improve gastrointestinal cancer survival is screening and treatment of the early lesions. In esophageal adenocarcinoma, there is increasing thought 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 has therefore been devoted to discover molecular biomarkers of "high-risk" states and develop imaging tools for detecting these biomarkers in a manner that could assist the real-time in-vivo targeting of sites for biopsy. The strategy we have employed is to generate stem cell clones from Barrett's esophagus biopsies and 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 datasets 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, making real-time diagnosis, stratifying patients during the examination, and ultimately directing therapy in a preemptive manner. This review will focus on Barrett's esophagus and its associated neoplasia to illustrate the utility of biomarker and molecular imaging in aiding targeted biopsy, making real-time diagnosis, stratifying lesions during examination, and directing treatment of this gastrointestinal disorder during surveillance endoscopy.