The ASPIRE Path in Molecular Medicine

Colorectal cancer (CRC) is the third most common and second most lethal cancer. About 20% of patients are diagnosed with metastatic disease. These individuals will experience no signs or symptoms until it is discovered at a late stage. Unfortunately, the 5-year survival rate for stage IV CRC is only 14%. However, the addition of targeted therapies has improved overall survival rates. Cetuximab is a monoclonal antibody used to inhibit EGFR in KRAS wild-type metastatic CRC. Sadly, all responding patients will eventually develop resistance to this targeted therapy. Metabolic dysregulation is one of the most common hallmarks of cancer and increased glutamine metabolism is frequently observed in cancer as it is needed for proliferation and survival. Glutamine is transported into the cell and is converted to glutamate by mitochondrial glutaminase. Glutamate is used to make ATP and contributes to tumor progression. My goal is to understand the role of the glutamate transporter, SLC1A7, and subsequent glutamate metabolism in CRC progression and cetuximab resistance. This enhanced knowledge of glutamate’s role in cancer resistance and progression will help guide us to design and test novel combination therapies that may overcome anti-EGFR resistance in cancer treatment for CRC.