Grant: Project Grant

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 investigating which genes are consistently present at higher levels in more advanced metastatic breast cancers which contribute to cancer progression and metastasis. We have found that knocking down one of these cancer promoting genes gives the desired effect of reducing triple negative breast cancer progression and metastasis. These and other results validated it as an excellent new target for metastatic breast cancer. Since there are no known inhibitors for this target gene product, we used computer modeling to identify a panel of likely inhibitors and experimental testing successfully identified several hit compounds that are good inhibitors. Several highly related compounds were chemically generated and showed even stronger inhibitory properties. In this project, we will generate, and test compounds closely related to these lead compounds to find the most suitable drug-like compound. The most promising inhibitor will then be tested for its effectiveness at reducing cancer cell growth and metastasis in laboratory 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.