Defining the Role of Renal Gluconeogenesis in Renal Cell Carcinoma

PROJECT SUMMARY Renal cell carcinoma is the most common primary kidney cancer, representing 90-95% of primary renal neoplasms. Our work in the parent award has identified a novel liver-brain-adipose tissue-kidney gluconeogenesis axis that drives renal cell carcinoma, driven by fibroblast growth factor (FGF)-21. While

completing studies in the parent award, we became aware that our murine models of RCC exhibit cancer cachexia, with striking loss of skeletal muscle. Cancer cachexia is a widespread and debilitating problem, and the work proposed in this supplement will test the hypothesis that FGF-21-driven renal gluconeogenesis

may be a key contributor to cachexia in renal cell carcinoma. The candidate, Andin Fosam, is an African American, first generation American citizen who aims to become a physician-scientist leading a translational research program at the intersection between oncology and preservation of functional status. The work

proposed in this supplement application will position Andin, an M.D./Ph.D. student completing her doctoral work in the PI's lab, as a growing leader in this multifaceted area, which is in deep need of new investigators to push the boundaries of our understanding of how physiologic principles can help avoid the devastating

consequences of cancer cachexia.