Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R01 Clinical Trial Optional) | PAR 23 279

Opportunity Information: Apply for PAR 23 279

The National Institutes of Health (NIH) is offering an R01 grant opportunity titled "Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R01 Clinical Trial Optional)" (Funding Opportunity Number PAR-23-279; CFDA 93.393). This discretionary grant focuses on understanding how incretin mimetic therapies, including GLP-1 agonists or antagonists, GIP-1 agonists or antagonists, and dual GLP-1/GIP-1 agents, may influence cancer risk. The main point is not to re-test short-term outcomes that are already commonly studied (like weight loss, glycemic control, or near-term metabolic improvements), but to dig into the biological mechanisms that could explain why these drugs might change cancer risk in different directions depending on the cancer type.

The funding announcement has two core goals. First, it aims to stimulate both preclinical and patient-based research that directly examines the mechanism(s) through which incretin mimetics affect cancer risk. That includes laboratory work that can establish causality and identify pathways, as well as human-focused studies that can connect drug exposure to meaningful biological changes in tissues, immune function, endocrine signaling, inflammation, or other cancer-relevant processes. Second, NIH is explicitly trying to pull in investigators who already understand the complex and dynamic physiological shifts caused by incretin mimetics and encourage them to apply that expertise to cancer biology questions, rather than staying limited to the traditional diabetes and obesity endpoints.

A key rationale for the opportunity is the emerging, mixed picture in the existing evidence base. Available data suggest that incretin mimetics could potentially increase the risk of some cancers while decreasing the risk of other cancers, particularly within the group of cancers associated with obesity. This creates an urgent need to move beyond correlation and establish plausible mechanistic explanations. In practice, NIH is signaling strong interest in research that can disentangle direct drug effects from indirect effects mediated by weight loss, insulin and IGF signaling changes, altered nutrient handling, shifts in bile acids, chronic inflammation changes, microbiome effects, or immune modulation. The emphasis on "mechanisms" means projects should be designed to explain the "how" and "why" behind cancer risk changes, rather than simply reporting whether a risk signal exists.

The mechanism emphasis also implies that strong applications will likely integrate more than one line of evidence, such as pairing animal or cellular models with patient biospecimens, using molecular profiling to map pathway changes, or leveraging clinical datasets in ways that are tied to biological hypotheses. Because the announcement is labeled "Clinical Trial Optional," applicants are not required to run a clinical trial, but they may include one if it is justified by the mechanistic aims. That flexibility supports a wide range of study designs, from bench science through translational studies and carefully targeted clinical investigations.

Eligibility is broad and includes many types of U.S. organizations, such as state, county, city, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; and other tribal organizations. It also includes public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and an "other" category that typically captures additional entities allowed under NIH policy. The announcement also highlights additional eligible applicants that NIH often encourages to apply, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. (foreign) organizations.

The opportunity was created on August 23, 2023, and lists an original closing date of January 7, 2027. While the award ceiling and expected number of awards are not specified in the provided source data, the mechanism being an R01 generally indicates support for substantial, multi-year research projects with a clear hypothesis-driven structure, rigorous methods, and a strong plan for producing actionable mechanistic insight. Overall, NIH is using this announcement to accelerate high-quality science that clarifies whether, when, and through what pathways incretin mimetics may alter cancer risk, with the longer-term goal of improving patient safety, guiding clinical decision-making, and informing future drug development and risk mitigation strategies.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.393.
• This funding opportunity was created on 2023-08-23.
• Applicants must submit their applications by 2027-01-07.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 23 279

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: