Grant Award Summary

The National Cancer Institute (NCI), under the Cancer Cause and Prevention Research program (CFDA 93.393), awarded a $658,093 Project Grant to the University of North Carolina at Chapel Hill effective July 13, 2026, with a completion date of June 30, 2031. This research initiative investigates mechanisms by which obesity drives endometrial cancer development and progression, with a focus on evaluating pharmacological and dietary weight-loss interventions as cancer prevention strategies. The project will examine how incretin mimetics—specifically tirzepatide (a dual GLP-1/GIP receptor agonist) and retatrutide (a triple GLP-1/GIP/glucagon receptor agonist)—as well as intermittent energy restriction protocols can mitigate obesity-associated tumor growth in preclinical models and reverse the metabolic and immunological dysfunction that characterizes the obese state.

The funded research will establish the direct and indirect anti-tumorigenic mechanisms of these weight-loss interventions by evaluating their effects on insulin signaling, lipid metabolism, mTOR pathway activation, and immune cell function in endometrial tissue and tumor microenvironments. Deliverables will include mechanistic data characterizing how tirzepatide and intermittent energy restriction inhibit endometrial intraepithelial neoplasia and cancer progression, with potential to support future translational studies and inform cancer prevention strategies targeting the obesity-endometrial cancer axis. The five-year project period supports hypothesis-driven basic research aligned with NCI's strategic priorities in cancer chemoprevention and mechanistic understanding of carcinogenesis.