Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) invites applications for support of investigator-initiated studies addressing mechanisms by which bariatric surgery impacts cancer risk, and seeks to draw in talented scientists who study bariatric surgery to investigate its effects on cancer, rather than shorter-term outcomes such as weight loss and diabetes.The National Cancer Institute (NCI) is offering funding for research on the mechanisms by which bariatric surgery affects cancer risk. Through this R01 grant opportunity, researchers are encouraged to explore how bariatric surgery, beyond weight loss, may impact cancer outcomes, including the roles of biological mechanisms such as changes in bile acids, gut microbiota, and immune system interactions. This funding opportunity is intended to draw investigators interested in the long-term health effects of bariatric surgery beyond metabolic improvements, including its impact on cancer incidence, mechanisms of cancer risk reduction, and surgery-specific effects.

Bariatric surgery, which currently is the most effective intervention for sustained weight loss in morbidly obese individuals, has shown promise in reducing the risk of several cancers. This NOFO encourages studies to clarify whether the benefits derive from weight loss alone or if surgery-specific changes contribute uniquely to reduced cancer risk. Research may focus on mechanisms involving bile acid metabolism, shifts in gut microbiota, and cellular or metabolic processes altered post-surgery. Additionally, studies may consider whether gender, surgical type (e.g., sleeve gastrectomy versus Roux-en-Y gastric bypass), and ethnic background influence cancer outcomes, as well as investigate the differential impact of these surgeries on specific cancer types.

Proposals should focus on mechanistic research, supported by animal models or human biospecimens from established cohorts such as the Longitudinal Assessment of Bariatric Surgery (LABS) and other resources. Investigations must aim for insights that explain cancer incidence or recurrence post-surgery, moving beyond epidemiological approaches and into biological mechanisms. Non-responsive applications include those focusing exclusively on epidemiological endpoints or in vitro studies without in vivo tissue samples. Additionally, projects that propose clinical trials without the involvement of a bariatric surgeon as a key investigator will not be reviewed.

This grant opportunity allows for a maximum budget of $500,000 in direct costs per year, with a project period of up to five years. Both new applications and resubmissions are accepted. Eligible applicants include higher education institutions, nonprofits, for-profit entities, and government bodies within the U.S., though foreign entities cannot apply. Applications are due on standard NIH due dates, with the earliest submission on February 5, 2025. A letter of intent is encouraged but not required, due 30 days before the application deadline.

Applications will be evaluated based on three main criteria: the significance of the research to advance cancer knowledge, the rigor and feasibility of the approach, and the expertise and resources of the investigative team. Special consideration will be given to applications with a clear focus on the link between bariatric surgery and cancer outcomes, particularly those investigating mechanisms with potential translational impact. Furthermore, applications that propose multidisciplinary collaborations, particularly with experts outside of traditional cancer research fields, will receive special consideration in programmatic review.

Prospective applicants are encouraged to consult with NCI staff at least 12 weeks before submission to align their research proposal with NOFO priorities. The final review will assess factors including the study's potential to provide reproducible, impactful results and the institutional resources available to support successful project execution. Selected proposals will undergo NIH peer review, and awardees will be required to submit annual performance reports.

This funding opportunity aligns with NCI’s mission to support research into cancer prevention and treatment and to understand the broader health impacts of metabolic interventions like bariatric surgery.