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.
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.
| Malone, Clare F; Emerson, Chloe; Ingraham, Rachel et al. (2017) mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors. Cancer Discov 7:1450-1463 |
| Maertens, Ophélia; McCurrach, Mila E; Braun, Benjamin S et al. (2017) A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies. Cancer Res 77:5706-5711 |
| Olsen, Sarah Naomi; Wronski, Ania; Castaño, Zafira et al. (2017) Loss of RasGAP Tumor Suppressors Underlies the Aggressive Nature of Luminal B Breast Cancers. Cancer Discov 7:202-217 |
