Mercedes Rincon

Equity Interest - Non-publicly traded entity ( e.g., stock, stock option, or other ownership interest)

A novel target to overcome chemoresistance in breast cancer

NARRATIVE About 40,000 women die each year from breast cancer in the US due to development of chemoresistance. Chemotherapy is still one of the most effective and widely used means of treating breast cancer. More than one third of the breast cancer patients are dependent on chemotherapy as the only available treatment (including those who are already diagnosed with metastatic cancer). Thus, there is clear unmet need to overcome chemoresistance in breast cancer patients. One of the mechanism by which breast cancer cells become resistant to chemotherapy is the use of drug efflux pumps that send the chemotherapeutic drugs outside of the cells to protect them from death. These pumps (called ABC transporters) use a lot of energy in the form of ATP to pump drugs outside of the cells. Our recent studies indicate that the ATP used as source of energy for these pumps is generated by mitochondria, intracellular organelles that act as engine of the cells. Thus, to overcome chemoresistance we propose to reduce the energy (ATP) produced by mitochondria (engine of the cancer cells). We have recently discovered that some cancer cells have lost a new molecule, MCJ, that we have identified as a brake for mitochondria. As a result, the engine (mitochondria) of those MCJ- deficient cancer cells has more power, makes more ATP (energy) and as a consequence the drug efflux pumps are more active and the cells are more resistant. We have developed new compounds (MCJ mimetics) that restore MCJ function in those cells that have lost it. Basically MCJ mimetics act as alternative brakes of the mitochondria, to reduce the ATP used by the pumps. Our preliminary studies support that these MCJ mimetics could be used as therapeutics to overcome chemoresistance to standard chemotherapeutic drugs used for breast cancer patient treatment.