Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R01 Clinical Trial Optional) | PAR 25 069

Opportunity Information: Apply for PAR 25 069

The NIH funding opportunity "Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R01 Clinical Trial Optional)" (PAR-25-069) is an R01 grant program focused on understanding how incretin mimetic drugs may change cancer risk. The central emphasis is on mechanism, meaning applicants are expected to investigate the biological pathways and causal processes through which these agents influence cancer initiation, progression, or prevention. The program is intentionally aimed at moving the field beyond short-term clinical outcomes that often dominate incretin mimetic research, such as weight loss and glycemic control, and toward deeper, cancer-relevant mechanistic insight.

The announcement highlights incretin mimetics broadly, including agonists or antagonists of GLP-1 and GIP-1, as well as dual GLP-1/GIP-1 agents. These drugs have rapidly expanded in use for diabetes and obesity, which makes clarifying their long-term cancer implications a pressing public health question. The opportunity is framed around a key observation motivating the research need: existing data suggest the possibility of mixed effects, where incretin mimetics might increase the risk of certain cancers while decreasing the risk of other obesity-associated cancers. Because obesity itself is linked to multiple cancer types, and because incretin mimetics can produce complex and dynamic physiologic changes, the NIH is seeking studies that can disentangle direct drug effects from indirect effects mediated by weight loss, metabolic improvements, inflammation changes, hormonal shifts, immune modulation, or tissue-specific signaling.

Projects responsive to this call can include both preclinical and patient-based research. Preclinical studies may use in vitro systems, animal models, or other experimental platforms suited to pinpointing mechanisms. Patient-based studies may leverage clinical samples, biospecimens, molecular profiling, clinical pharmacology, or observational and translational approaches that illuminate how these drugs alter cancer-relevant pathways in humans. The "Clinical Trial Optional" designation means applicants may propose a clinical trial if it is scientifically justified, but a trial is not required; mechanistic human studies can be designed with or without an interventional component, depending on the research question.

A major goal of the announcement is also talent-focused: it aims to attract investigators who already understand the broad physiologic and metabolic changes caused by incretin mimetics and encourage them to apply that expertise to cancer biology questions. In practice, this signals interest in multidisciplinary teams that can connect endocrinology, metabolism, pharmacology, immunology, molecular oncology, and epidemiology, while still maintaining a clear mechanistic through-line. The NIH is essentially encouraging applicants to explain not just whether a risk signal exists, but why it might exist, in which tissues or patient subgroups, and through which pathways.

The opportunity is offered by the National Institutes of Health under CFDA number 93.393, categorized under Education and Health, using the discretionary grant mechanism (R01). The original closing date listed is January 7, 2027, with the opportunity created on November 18, 2024. Award ceiling and expected award counts are not specified in the provided listing, which often means applicants should consult the full FOA text or NIH institute budget guidance for typical R01 ranges and any institute-specific considerations.

Eligibility is broad and includes many types of U.S. organizations and governments: state, county, city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; public housing authorities/Indian housing authorities; federally recognized Native American tribal governments; tribal organizations other than federally recognized governments; nonprofits with and without 501(c)(3) status (excluding institutions of higher education when specified); for-profit organizations other than small businesses; and small businesses. The announcement also explicitly calls out additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), 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 even non-U.S. entities (foreign organizations). This broad eligibility aligns with the NIH interest in pulling in diverse scientific perspectives and ensuring that research capacity across many institution types can contribute to answering an urgent and widely relevant question.

Overall, the grant is best understood as a call for rigorous, mechanistically driven cancer research centered on incretin mimetic therapies that are increasingly common in clinical practice. The NIH is signaling that the field needs clearer causal explanations for how GLP-1/GIP-related agents might raise or lower cancer risk, and it is willing to support both foundational experimental work and carefully designed human studies to get there.

• 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 2024-11-18.
• 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 25 069

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