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)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Agarwal, Rajeev K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Case Western Reserve University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Chak, Amitabh; Buttar, Navtej S; Foster, Nathan R et al. (2015) Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett's esophagus. Clin Gastroenterol Hepatol 13:665-72.e1-4
Sanchis-Gomar, Fabian; Lucia, Alejandro; Yvert, Thomas et al. (2015) Physical inactivity and low fitness deserve more attention to alter cancer risk and prognosis. Cancer Prev Res (Phila) 8:105-10
Luo, Yanxin; Wong, Chao-Jen; Kaz, Andrew M et al. (2014) Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer. Gastroenterology 147:418-29.e8
Fink, Stephen P; Yamauchi, Mai; Nishihara, Reiko et al. (2014) Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD). Sci Transl Med 6:233re2
Koon, Henry B; Krown, Susan E; Lee, Jeannette Y et al. (2014) Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol 32:402-8
Corradin, Olivia; Saiakhova, Alina; Akhtar-Zaidi, Batool et al. (2014) Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res 24:1-13
Hao, Yujun; Zhao, Shuliang; Wang, Zhenghe (2014) Targeting the protein-protein interaction between IRS1 and mutant p110* for cancer therapy. Toxicol Pathol 42:140-7
Cummings 3rd, Kenneth C; Patel, Meatal; Htoo, Phyo Than et al. (2014) A comparison of the effects of epidural analgesia versus traditional pain management on outcomes after gastric cancer resection: a population-based study. Reg Anesth Pain Med 39:200-7
Alashkar, Bronia; Faulx, Ashley L; Hepner, Ashley et al. (2014) Development of a program to train physician extenders to perform transnasal esophagoscopy and screen for Barrett's esophagus. Clin Gastroenterol Hepatol 12:785-92
Scott, Anthony; Song, Jing; Ewing, Rob et al. (2014) Regulation of protein stability of DNA methyltransferase 1 by post-translational modifications. Acta Biochim Biophys Sin (Shanghai) 46:199-203

Showing the most recent 10 out of 32 publications