Exploiting lipid metabolism and dietary interventions to sensitize kras-driven tumors to ferroptosis

The National Cancer Institute awarded a $672,300 Cooperative Agreement to the University of Cincinnati's Sponsored Research Services Division on September 1, 2026, under the Cancer Biology Research program (CFDA 93.396) to conduct preclinical research on how dietary and therapeutic interventions influence tumor development, progression, and treatment response in lung, pancreatic, and colorectal cancers driven by KRAS mutations and sensitive to ferroptosis.

The research integrates human tumor xenografts, immunocompetent syngeneic models, and genetically engineered mouse models that reproduce key oncogenic alterations and histopathologic features of the corresponding human diseases. Both male and female mice will be evaluated with age-matched controls to assess tumor growth, treatment response, metabolic adaptation, and contributions from the tumor microenvironment. Tumor establishment and progression will be monitored using micro-computed tomography and colonoscopy, with interventions initiated according to predefined tumor-size criteria. Experimental group sizes are supported by power calculations to provide adequate statistical power while limiting animal use.

The award runs through August 31, 2031, with performance at the Cincinnati, Ohio campus. The Cooperative Agreement mechanism reflects NIH's expectation of substantive federal involvement in planning and direction beyond typical grant funding.

Abstract

This project will determine how dietary and therapeutic interventions influence tumor development, progression, and treatment response in lung, pancreatic, and colorectal cancers. Studies will integrate human tumor xenografts, immunocompetent syngeneic models, and genetically engineered mouse models that reproduce key oncogenic alterations and histopathologic features of the corresponding human diseases. Both male and female mice will be used, with age-matched controls, to evaluate tumor growth, treatment response, metabolic adaptation, and contributions from the tumor microenvironment. Tumor establishment and progression will be monitored using appropriate imaging and endoscopic approaches, including micro-computed tomography and colonoscopy, and interventions will be initiated according to predefined tumor-size criteria. Experimental group sizes are supported by power calculations and have been selected to provide adequate statistical power while limiting animal use. Vertebrate animals are required because two-dimensional cell-culture systems cannot reproduce the systemic interactions among diet, whole-body metabolism, tumor genetics, stromal components, immune responses, and treatment exposure that determine tumor growth and therapeutic response in vivo. The complementary use of xenograft, syngeneic, and genetically engineered models will permit evaluation of both tumor-cellintrinsic and host-dependent mechanisms while reducing the number of genetically engineered animals required and maintaining the biological and translational relevance of the study.