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

Li, Yuguo; Qiao, Yuan; Chen, Hanwei et al. (2018) Characterization of tumor vascular permeability using natural dextrans and CEST MRI. Magn Reson Med 79:1001-1009
Saung, May Tun; Muth, Stephen; Ding, Ding et al. (2018) Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer. J Immunother Cancer 6:118
Canto, Marcia Irene; Almario, Jose Alejandro; Schulick, Richard D et al. (2018) Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. Gastroenterology 155:740-751.e2
Makohon-Moore, Alvin P; Matsukuma, Karen; Zhang, Ming et al. (2018) Precancerous neoplastic cells can move through the pancreatic ductal system. Nature 561:201-205
Chu, Nam; Salguero, Antonieta L; Liu, Albert Z et al. (2018) Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis. Cell 174:897-907.e14
Felsenstein, Matthäus; Noë, Michaël; Masica, David L et al. (2018) IPMNs with co-occurring invasive cancers: neighbours but not always relatives. Gut 67:1652-1662
Grant, Robert C; Denroche, Robert E; Borgida, Ayelet et al. (2018) Exome-Wide Association Study of Pancreatic Cancer Risk. Gastroenterology 154:719-722.e3
Tie, Jeanne; Cohen, Joshua D; Wang, Yuxuan et al. (2018) Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut :
Adler, B L; Pezhouh, M K; Kim, A et al. (2018) Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis. J Intern Med 283:568-577
Ma, Qianqian; Gabelli, Sandra B; Raben, Daniel M (2018) Diacylglycerol kinases: Relationship to other lipid kinases. Adv Biol Regul :

Showing the most recent 10 out of 883 publications