Barrett's esophagus translational research network (BETRNet): The pivotal role of multi-institutional collaboration in esophageal adenocarcinoma research

The incidence of esophageal adenocarcinoma (EAC) has been increasing steadily over the past few decades,1 despite widespread recognition of the problem and a vast body of research. This disease is believed to originate in the broadest sense from Barrett’s Esophagus (BE), the recognized precursor of EAC, but current methods for surveillance have not been found to be effective in defining patients at risk. While a number of molecular and cellular mechanisms that underlie the transformation of BE to EAC have been outlined, their utility in understanding and preventing the progression of this cancer or in managing the intervention-resistant clones has not been demonstrated in a number of proposed models. As the rate of progression of BE to EAC is very low, estimated at <0.5% per year,2–4 individual investigators rarely have access to a sufficient number of biospecimens or clinical data to rigorously validate their models in longitudinal studies. A multi-institutional approach that combines novel scientific resources is envisioned to be essential for elucidating early biological events that drive EAC formation, understanding the role of the precursor lesion BE including its cell of origin, and devising unique preventive methods. The need for meaningful collaborations for conducting multi-disciplinary and multi-institutional studies was identified by the Barrett’s Esophagus Working Group in 2001, the Stomach/Esophageal Cancers Progress Review Group in 2002 and then further crystallized by the Barrett’s Esophagus Translational Research Working Group Meeting convened by the National Cancer Institute (NCI) in 2008. It became clear from these and other efforts that in order to address the challenge of EAC, understand the intricacies of the Barrett’s neoplasia, and facilitate the development of more translational strategies for early detection and prevention, it was imperative to create a trans-disciplinary team with key scientific expertise to “jump start” progress in this field. To that end, NCI formed the Barrett’s Esophagus Translational Research Network (BETRNet) in 2011, a program that is jointly funded through a cooperative agreement by the Division of Cancer Biology and the Division of Cancer Prevention (http://prevention.cancer.gov/programs-resources/programs/betrnet and https://dcb.nci.nih.gov/Pages/Programs.aspx). BETRNet encompasses three Research Centers, each representing a network of networks, and a Coordinating Center (Fig. 1). The translational Research Centers are headquartered at Columbia University, University of Michigan and Case Western Reserve University, and Coordinating Center is located at Vanderbilt University. The Research Centers are primarily focused on discovering biological pathways that trigger the development of BE and EAC, using state-of-the-art experimental models and human specimens for translation into early cancer detection, risk stratification and prevention strategies. The Coordinating Center functions to integrate cross-network activities with emphasis on a network-wide virtual biorepository. Through collective leveraging of novel animal and cellular models, genomics, proteomics and imaging as well as access to biospecimens, BETRNet is employing the concept of true team-based science to answer some of the “big” and most puzzling questions in EAC research. Fig. 1 BETRNet