This Case Gl SPORE proposal provides for a cutting edge Specialized Program of Research Excellence in gastrointestinal malignancies with emphasis on colorectal cancers and with additional attention to adenocarcinoma of the esophagus. This comprehensive program builds on the resources of the Case Comprehensive Cancer Center to propose 4 translational Research Projects to bring new molecular advances to patients with Gl Cancers. A series of 4 core resources support these research projects and also establish a strong programmatic infrastructure for translational research in Gl cancers. We further have developed a comprehensive infrastructure for identifying new Developmental Research Projects from basic science and clinical investigators from across the Case Cancer Center. Moreover, drawing on our strong track record of developing new faculty who emphasize translational research in Gl cancers, we propose a targeted Career Development Program to further enhance the translational research cadre of SPORE faculty. The 4 SPORE translational research projects constitute novel and cutting edge approaches to Gl cancers and include studies of: the predictive, prognostic, and therapeutic applications of the new 15-PGDH colon cancer suppressor pathway (Project 1, Drs. Markowitz and Willson);the noninvasive early detection of advanced colon adenomas through stool DNA testing for methylated DNA (Project 2, Drs. Cooper and Li);the comprehensive evaluation of colon cancer gene mutations as predictors of clinical outcome, via use of high throughput Next Generation genomic sequencing (Project 3, Drs. Willis and Wang);and the identification of esophageal adenocarcinoma susceptibility genes (Project 4, Drs. Chak and Elston). These projects are advantaged by special population and scientific resources developed by our SPORE faculty for: evaluation of colon cancer biomarkers, for high throughput screening for new drug discovery, for evaluation of colon cancer screening modalities, for Next Generation sequencing from archived formalin fixed tissue samples, and for study of familial Barrett's and adenocarcinomas of the esophagus. The strength of these investigators and the resources at their disposal will ensure this program leads to important advances.

Public Health Relevance

Colon cancers are the second leading cause of cancer death in adult Americans, and esophageal adenocarcinomas are the most rapidly increasing cause of cancer deaths in adult Americans. This Case Gl SPORE proposal focuses cutting edge scientific resources on the theme of identifying and clinically applying molecular cancer biomarkers in order to reduce deaths from these diseases.

National Institute of Health (NIH)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Agarwal, Rajeev K
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Case Western Reserve University
Internal Medicine/Medicine
Schools of Medicine
United States
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Kendall, Bradley J; Rubenstein, Joel H; Cook, Michael B et al. (2016) Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis. Clin Gastroenterol Hepatol 14:1412-1419.e3
Thota, Prashanthi N; Zackria, Shamiq; Sanaka, Madhusudhan R et al. (2016) Racial Disparity in the Sex Distribution, the Prevalence, and the Incidence of Dysplasia in Barrett's Esophagus. J Clin Gastroenterol :
Parameswaran, Reshmi; Ramakrishnan, Parameswaran; Moreton, Stephen A et al. (2016) Repression of GSK3 restores NK cell cytotoxicity in AML patients. Nat Commun 7:11154
Peyser, Noah D; Wang, Lin; Zeng, Yan et al. (2016) STAT3 as a Chemoprevention Target in Carcinogen-Induced Head and Neck Squamous Cell Carcinoma. Cancer Prev Res (Phila) 9:657-63
Cui, Min; Awadallah, Amad; Liu, Wendy et al. (2016) Loss of Hes1 Differentiates Sessile Serrated Adenoma/Polyp From Hyperplastic Polyp. Am J Surg Pathol 40:113-9
Venkitachalam, Srividya; Revoredo, Leslie; Varadan, Vinay et al. (2016) Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. Sci Rep 6:23642
Fecteau, Ryan E; Kong, Jianping; Kresak, Adam et al. (2016) Association Between Germline Mutation in VSIG10L and Familial Barrett Neoplasia. JAMA Oncol 2:1333-1339
Sun, Xiangqing; Elston, Robert C; Barnholtz-Sloan, Jill S et al. (2016) Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm. Cancer Epidemiol Biomarkers Prev 25:727-35
Russo, Suzanne; Ammori, John; Eads, Jennifer et al. (2016) The role of neoadjuvant therapy in pancreatic cancer: a review. Future Oncol 12:669-85
Eads, Jennifer R; Beumer, Jan H; Negrea, Lavinia et al. (2016) A pharmacokinetic analysis of cisplatin and 5-fluorouracil in a patient with esophageal cancer on peritoneal dialysis. Cancer Chemother Pharmacol 77:333-8

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