Grant: Project Grant - PA: Breast Cancer Research

Breast cancer affects one in nine Canadian women and those with metastatic breast cancer have a disheartening five-year survival rate of only 28%. Triple negative breast cancers lack the receptors for estrogen, progesterone and HER2 that are present in other types of breast cancer. Those receptors allow them to be targeted by specific therapies. Thus, the main treatment for triple negative breast cancer is chemotherapy which often has serious side effects. Having a targeted treatment option for triple negative breast cancer that is both effective and has reduced side effects is a current unmet clinical need. We have been studying a protein called CREB3L1. It is present in normal breast cells, but it is missing in highly metastatic breast cancers, including ~75% of triple negative breast cancers. The function of CREB3L1 is to block cells from making genes that increase cancer cell growth and metastasis. Therefore, when CREB3L1 is missing, these cancer promoting genes are present at higher levels and these can be targets for new treatments. We validated one of these genes as an excellent new target for metastatic breast cancer. Since there are no known inhibitors for this target gene product, we used computer modelling to identify a panel of likely inhibitors and successfully identified four hit compounds that are good inhibitors. In this project, we will generate, and test compounds closely related to these four hit compounds to find the most suitable drug-like compound that is not toxic to healthy cells. The most promising inhibitor will then be tested for its effectiveness at reducing cancer cell growth and metastasis in models of breast cancer. Our goal is to provide a new and more effective treatment for metastatic breast cancer with a focus on triple negative breast cancer. This novel therapy would have a significant positive impact on patient survival and will improve the health of Canadians diagnosed with metastatic breast cancer.