The National Cancer Institute (NCI) invites applications for exploratory and developmental studies under the "Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics" program (R21). This funding opportunity seeks to explore how glucagon-like peptide (GLP)-1 receptor agonists (RAs) and dual GLP-1/glucose-dependent insulinotropic peptide (GIP)-1 RAs influence cancer risk. The initiative targets pilot projects addressing mechanisms of cancer risk associated with these agents, widely used for type 2 diabetes mellitus (T2DM) and obesity, and supports innovative approaches to understand their potential protective or adverse effects on cancer.

This R21 program emphasizes short-term exploratory projects with a focus on basic science investigations. It offers funding for projects with budgets up to $275,000 in direct costs over two years, with no more than $200,000 in any single year. This mechanism is ideal for researchers initiating studies that may lead to larger-scale projects under the R01 companion NOFO. Clinical trials are not allowed under this funding opportunity.

Potential areas of investigation include evaluating how incretin mimetics modulate immune responses, metabolic pathways, or signaling molecules that may influence cancer risk. The program also welcomes studies assessing whether specific cancer types are more susceptible to these agents, exploring the roles of off-target effects, and investigating how demographic factors such as age, gender, or ethnicity alter outcomes. Both preclinical and human biomarker studies are appropriate, provided that mechanisms are evaluated using biological samples.

Eligible applicants include public and private higher education institutions, nonprofits, for-profit organizations, local governments, and foreign entities. Required registrations include SAM.gov, eRA Commons, and Grants.gov, and submissions must comply with NIH guidelines. Applicants are encouraged to submit letters of intent at least 30 days before the application deadline to facilitate review planning.

Applications are due on NIH standard deadlines: February 16, June 16, and October 16 annually. Proposals will be evaluated on their significance, innovation, approach, and feasibility, with particular emphasis on the potential for advancing understanding of cancer-related mechanisms impacted by incretin mimetics.

For detailed guidance, prospective applicants should review the NOFO and reach out to NCI contacts listed in the announcement. This program supports researchers aiming to generate new knowledge on the intersection of metabolic therapies and cancer biology, fostering innovative insights into disease prevention and treatment.