Abstract

Revised Abstract: The tremendous advances made in understanding the molecular details of cancer have so far failed to result in corresponding reductions in the mortality rates of the most common epithelial cancers. The goal of this project is to discover and apply emerging molecular genetic insights from colorectal cancer to rationally devise new strategies for blocking tumorigenesis. In work previously supported by the GI SPORE, a novel combinatorial chemopreventive strategy was developed using a combination of a potent irreversible inhibitor of epidermal growth factor receptor kinase and a low dose of the NSAID, sulindac. This combination proved to be particularly effective against intestinal tumors and was not associated with adverse side effects. The current proposal builds on this paradigm by proposing: 1) characterization of compounds and targets in mouse models, 2) mechanistic evaluation of molecular pathways, and 3) clinical evaluation of the most promising strategies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA062924-09
Application #
6670287
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Dejea, Christine M; Fathi, Payam; Craig, John M et al. (2018) Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359:592-597
Staedtke, Verena; Bai, Ren-Yuan; Kim, Kibem et al. (2018) Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome. Nature 564:273-277
Deng, Yang; Tu, Huakang; Pierzynski, Jeanne A et al. (2018) Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma. Eur J Cancer 92:20-32
Tamura, Koji; Yu, Jun; Hata, Tatsuo et al. (2018) Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer. Proc Natl Acad Sci U S A 115:4767-4772
Chung, Liam; Thiele Orberg, Erik; Geis, Abby L et al. (2018) Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe 23:203-214.e5
Nakamura, Hideki; Lee, Albert A; Afshar, Ali Sobhi et al. (2018) Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions. Nat Mater 17:79-89
Al Efishat, Mohammad A; Attiyeh, Marc A; Eaton, Anne A et al. (2018) Multi-institutional Validation Study of Pancreatic Cyst Fluid Protein Analysis for Prediction of High-risk Intraductal Papillary Mucinous Neoplasms of the Pancreas. Ann Surg 268:340-347
Cruz-Correa, Marcia; Hylind, Linda M; Marrero, Jessica Hernandez et al. (2018) Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology 155:668-673
Christmas, Brian J; Rafie, Christine I; Hopkins, Alexander C et al. (2018) Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs. Cancer Immunol Res 6:1561-1577
Blair, Alex B; Murphy, Adrian (2018) Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. Curr Probl Cancer 42:49-58

Showing the most recent 10 out of 883 publications