Eliminating Metastatic Triple-Negative Breast Cancer Through Ferroptosis
Abstract
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionately affects younger women and African American women and generally has a poorer prognosis than other breast cancer types. There are no effective targeted therapies for this aggressive disease in large part because our understanding of what molecular changes drive this breast cancer subtype is still so poor. There is currently tremendous interest in the possibility that cancer can be combatted by targeting the metabolism of cancer cells, which can differ significantly from normal cells. We recently discovered that TNBC cancer cells depend on a molecule called glutathione to survive, whereas normal breast cells are not as dependent on glutathione. TNBC cells need glutathione to avoid a form of cell death called ferroptosis that is linked to the cancer cells’ tendency to accumulate a certain type of fat molecule called polyunsaturated fatty acids. We discovered that administering certain polyunsaturated fatty acids selectively kills TNBC cells by ferroptosis, leaving normal cells unaffected. Importantly, we find that this type of fat reduces tumor growth and even slows metastasis in mouse models of TNBC. We believe that these specific polyunsaturated fatty acids can be used as an anti-tumor and anti-metastasis therapy in TNBC patients. We are very excited about these findings because: (1) The fatty acids that kill TNBC cells are naturally occurring components of certain food plants. They are inexpensive, can be taken orally, and are generally safe. (2) In addition to blocking tumor growth, they also block metastasis, the most feared and most deadly aspect of breast cancer. (3) This approach to targeting breast cancer metabolism is a very new and unprecedented concept and we are the first to show that breast tumor growth can be suppressed by triggering ferroptosis. (4) To our knowledge, we are the only lab to have identified the anti-TNBC activity of these fatty acids. The goal of this proposal is to optimize this therapy in preparation for clinical trials. Second, we propose to investigate exactly how they trigger cancer cell death so that we can identify patients most likely to benefit from this therapy. We think that this fatty acid therapy has the potential for revolutionizing the way TNBC is treated. This would represent a major breakthrough because the therapy for this devastating disease has been largely unchanged for decades. Critically, this therapy can be rapidly moved into clinical trials for TNBC patients who need this NOW.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910481
Entities
People
- Jeffrey R Peterson
Organizations
- United States Army