Grant: Operating Grant

Breast cancer development involves the activation of genes that promote tumour development (oncogenes) and the inactivation of genes that prevent it (tumour suppressor genes) through genetic changes such as gene mutations and chromosome rearrangements. Based on this, rationally designed therapies to inhibit proteins activated in breast cancer have entered clinical use. Two important examples are Herceptin and Lapatinib, which target the ErbB2 oncogene amplified in 20-30% of breast cancers. While these drugs are a major breakthrough, their use is plagued by lack of response in many patients and the inevitable emergence of drug resistance in most others. In this project we will use powerful new in vivo and in vitro models of breast cancer to study the function of c-Src a protein that regulates human breast cancers growth. We will identify genes that are epigenetically modified by c-Src and determine whether this is involved in breast cancer initiation and progression. We will also investigate the significance of a c-Src in other cell types that support breast cancer. Finally, we will test the hypothesis that c-Src is involved in the development of Herceptin and Lapatinib resistance, building on our initial observations that c-Src is significantly increased in breast cancer cells that have acquired resistance to targeted therapy. Our studies will clarify the role of c-Src in contributing to breast cancer and establish whether it can serve as a novel therapeutic target to improve treatments and outcomes for ErbB2-positive patients.