The Ras pathway is one of the most commonly deregulated pathways in human cancer. RAS genes are mutated in a broad spectrum of tumor types;however, RAS mutations are conspicuously absent in breast cancer, despite the fact that the pathway is hyperactivated. We have identified two RasGAP genes that appear to function as tumor suppressors in breast cancer. The goal of this application is to 1) understand how these proteins function and interact, 2) elucidate the mechanism by which these genes independently and cooperatively regulate breast cancer development, progression, and/or drug resistance, and 3) establish the frequency and clinical setting in which these genes are inactivated in human breast cancer. This work will serve as a basis for understanding why a subset of specific breast cancers progress, will elucidate novel aspects of Ras signaling, and will reveal how these new tumor suppressors link Ras to other signaling networks.

Public Health Relevance

The Ras pathway is one of the most commonly deregulated pathways in human cancer. However, RAS mutations are conspicuously absent in tumors such as breast cancer despite the fact that the pathway is hyperactivated. This grant aims to investigate two new human tumor suppressors in breast cancer, that function by regulating Ras and converging signaling pathways.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA188659-01
Application #
8767699
Study Section
Molecular Oncogenesis Study Section (MONC)
Program Officer
Lively, Tracy (LUGO)
Project Start
2014-09-18
Project End
2019-08-31
Budget Start
2014-09-18
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$331,419
Indirect Cost
$123,919
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115