PROJECT 005 – GASTROINTESTINAL CANCER RESEARCH PROGRAM PROJECT SUMMARY/ABSTRACT Taken together, gastrointestinal cancers (GI cancers) kill more patients per year than cancers from any other organ system. In 2019, 328,030 new GI cancers will be diagnosed, resulting in 165,460 deaths in the US. Additionally, many of the GI cancers are rising in incidence for a variety of reasons, such as the aging population, inflammation (pancreatic, gastric and esophageal cancers), human papillomavirus (anal cancer), hepatitis C, and non-alcoholic steatohepatitis (hepatocellular cancer), as well as unknown causes (neuroendocrine cancers). Vanderbilt-Ingram Cancer Center (VICC) has prioritized GI cancers into a research program because these diseases and their risk factors are more common and lethal in the catchment area, as well as the strength of VICC investigators in this field of research. Throughout its existence, the Gastrointestinal Cancer Research Program (GI) has been built on two core strengths: epidermal growth factor receptor (EGFR) signaling in metastatic colorectal cancer (mCRC) and the role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric cancer (GC). GI investigators continue to define mechanisms of resistance to EGFR targeted therapies and methods to overcome this resistance. GI members are ideally suited to conduct microbiome research, particularly H. pylori, its pathogenesis in GC, the differential sensitivity to H. Pylori carcinogenesis and the development of methods to prevent these cancers. Building on this core, GI has expanded its research across the spectrum of GI cancers, and members have extended their capabilities to understand, diagnose, prevent and treat GI cancers through intra-, inter-programmatic, and extramural collaborations. GI members seek to continue the Program's strong, longstanding track record of success through the study of processes underlying etiology, pathogenesis and progression; the exploration of the roles of infection, inflammation and immunity; studies of novel agents and diagnostic imaging modalities, treatment resistance mechanisms and biomarkers to improve patient outcomes; and translation of this new knowledge into clinical application. GI will also continue to mentor and train the next generation of GI cancer scientists. GI co-Leaders Cathy Eng, MD and R. Daniel Beauchamp, MD work to integrate the members' efforts within GI and VICC. They will work with GI members, other VICC research programs and the shared resources to continue fostering collaboration and conduct high impact cancer research. They will also encourage GI members to adopt and translate new technologies for greater clinical impact and continue successful recruitment strategies to engage new investigators in strategic areas prioritized by the Program. There are 35 members from eight departments and three schools with $9.6M in total peer-reviewed funding and NCI making up 49% ($4.7M); of 615 publications, 21% are intra-programmat...