The WVU Cancer Institute investigator in the Department of Biochemistry, Yehenew Agazie (DVM, PhD) receives a 5-year R01 grant from the National Cancer Institute (component institute of the NIH) to study alternative therapeutic strategies for the treatment of HER2-positive breast cancer. Overexpression of the human epidermal growth factor receptor 2 (HER2) is one of the causes of breast cancer. Although current anti-HER2 therapies are effective initially, cancer cells often develops resistance, leading to disease recurrence which is virtually incurable. The study focuses on identification of a new therapeutic target and invention of a new inhibitor (potential drug) against the new target. The project is based on prior work in the principal investigator’s (PI’s) laboratory that showed that targeting other molecules that play critical roles in HER2-posirtve breast cancer may provide better results. Particularly, the PI’s group has shown that inhibition of a protein called SHP2 blocks expression of the HER2 protein, the very cause of the disease, leading to differentiation of a cancer cell to a normal-looking breast epithelial cell. Dr. Agazie has already invented an anti-SHP2 compound and obtained a patent. The anti-breast cancer effect of this compound will be studied in model mice and patient-derived xenograft tumors. The long term goal is to come up with a lead compound for developing anti-SHP2 drugs. Drs. Lockman, Rojanasakul, and Wen are co-investigators in the project.