Mutations in codon 12, 13, or 61 convert H-ras, K-ras, and N-ras into oncogenes. Such mutationally activated Ras proteins are found in about 30% of human tumors. Despite their medical importance, specific therapeutic agents directly targeting Ras proteins have not yet been discovered. To develop such Ras inhibitors, we have identified peptide aptamers that interact with oncogenic RasV12 from human tumors. Furthermore, we have demonstrated that these peptide aptamers inhibit the Ras/Raf signal transduction pathway in mammalian cells. Moreover, we have shown that these Ras peptide aptamers inhibit tumor growth in vitro and in mice bearing human tumor xenografts. Here, we propose to further characterize: 1. Peptide aptamers that inhibit Ras functions. 2. Peptide aptamers that interact with oncogenic Ras. 3. Peptide aptamers that inhibit tumorigenesis. These studies provide a new systematic framework for developing inhibitors of any proteins of biological and/or medical importance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA108795-05
Application #
7642406
Study Section
Drug Discovery and Molecular Pharmacology Study Section (DMP)
Program Officer
Forry, Suzanne L
Project Start
2005-07-01
Project End
2010-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
5
Fiscal Year
2009
Total Cost
$337,007
Indirect Cost
Name
Nevada Cancer Institute
Department
Type
DUNS #
557447690
City
Las Vegas
State
NV
Country
United States
Zip Code
89135
Yamazaki, Hiroto; Xu, C Wilson; Naito, Motohiko et al. (2011) Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia. Biochem Biophys Res Commun 409:14-21