Institution: UPR – Humacao Campus

Email: marcos.lopez11@upr.edu

Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer. TNBC tumors are not responsive to standard endocrine therapies and often exhibit resistance. For patients with metastatic disease, the median overall survival is estimated to be less than 18 months. Thus, there is a critical unmet need for new therapies to treat patients with TNBC. Advancing research in cancer therapy is focused on exploiting the biochemical differences between cancer and normal cell metabolism. Emerging evidence has shown that distinct tumor-specific metabolic changes, including reliance on aerobic glycolysis and changes in mitochondrial bioenergetics, are critical drivers of malignancy in TNBC. Previously, we
demonstrated that mitochondrial metabolism and reactive oxygen species (ROS) are essential for tumorigenicity. In addition, it has been reported that TNBC cells exhibit elevated glycolysis and increased generation of ROS compared to non-TNBC cells. The main goal of this project is to develop new therapeutic approaches to inhibit TNBC by targeting mitochondrial metabolism and bioenergetics. The significance of the proposed work lies in the use of relatively non-toxic mitochondria-targeted SG-1 nitroxide that disrupts mitochondrial metabolism and bioenergetics to inhibit TNBC cell proliferation and metastasis. First, we will assess the efficacy of Mito-SG1 in TNBC tumor cells. Then, we will use innovative extracellular flux analyses (Seahorse XFe-96) to investigate bioenergetic changes in human TNBC cells. Finally, we will screen the in-vivo efficacy of Mito-SG1 to mitigate TNBC. Successful completion of these aims will increase our understanding of the role of metabolism, mitochondrial bioenergetics, and energysensing in TNBC cancer malignancy.