2024-25 Team Science Grantees: Sammy Ferri-Borgogno, PhD, Samuel C. Mok, PhD & Deepak Nagrath, PhD
About Project
Targeting Glutamine in Ovarian Cancer Prevention
PROJECT SUMMARY
Epithelial ovarian cancer is the most predominant subtype of ovarian cancer. Besides the highly penetrant BRCA1/2 mutations which confer large increases in ovarian cancer risk, additional causes of ovarian cancer are yet to be identified. More research is needed to better understand the heterogeneous etiology of this deadly disease. Our recent studies showed that one glutamine molecule produced by the supporting cells in ovarian cancer can promote cancer progression and metastasis. Feeding mice with a glutamine-free diet or treating mice with an inhibitor targeting glutamine production significantly reduced the tumor in ovarian cancer-bearing mice. These findings suggest that the glutamine-free diet or the glutamine inhibitor can also prevent the development of ovarian cancer and prevent early-stage cancer cells from metastasizing from the oviduct, which corresponds to the human fallopian tube. We propose to use a new mouse model in which tumors can be induced to form in the oviduct and subsequently metastasize to the ovaries and other pelvic and abdominal sites to test this idea. Mice will be either fed with the glutamine-free diet or treated with the inhibitor, and the number of mice developing microscopic tumors in the oviducts in a certain period of time will be determined. The distribution of various immune cell types, metabolites (products of natural intracellular reactions), and mRNAs in the oviducts of mice fed with the glutamine-free diet or treated with the inhibitor will also be compared with their corresponding controls. Findings from this study will provide new insights into strategies for better prevention and early detection of ovarian cancer.
