Grant: CIHR - ICR / Cancer Research Society Partnership - Res. Grants - Breast Cancer

Breast cancer is the most common malignancy among women, and remains the second-leading cause of cancer-related mortality in the female population. There are several breast cancer subtypes, and one of them is represented by triple-negative breast cancer (TNBC) tumors. TNBC is associated with high patient mortality, which is at least in part due to the complete absence of clinically relevant targeted therapies. Therefore, there is an urgent need to identify effective therapeutic targets for treating TNBC cancer. A specific group of cancer cells called tumor-initiating cells (TICs) is responsible for the development, maintenance and aggressiveness of tumors, and thus their elimination is crucial for curing this malignancy. Our recent findings show that the fragmentation of the mitochondrial network plays a crucial role in supporting TIC activity in TNBC. This suggests that molecules that induce this response may be used as efficient targets for TNBC therapy, as their inhibition would allow one to eliminate TICs and thus eradicate TNBC tumors. Based on this, we propose to identify molecular mechanisms that drive mitochondrial fragmentation specifically in TNBC TICs, and to examine if inhibition of these molecular mechanisms indeed kills these cells and suppresses tumor growth in animal models of human TNBC. Overall, our investigation is expected to identify effective targets for TNBC therapy and to support the development of new efficient approaches for treating this malignancy.