PAR-25-070
Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R21 Clinical Trial Not Allowed)
Summary
PAR-25-070: Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics
Research Focus
This R21 Exploratory/Developmental Research Grant from the National Cancer Institute (NCI) seeks investigator-initiated studies examining how incretin mimetics—specifically glucagon-like peptide (GLP)-1 receptor agonists (RAs) or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP)-1 RAs—alter cancer risk through mechanistic pathways. The funding targets an understudied but clinically urgent problem: these agents are increasingly prescribed for type 2 diabetes mellitus (T2DM) and obesity (a $11.3 billion market growing >6% annually), yet their effects on cancer incidence remain poorly characterized. Preliminary evidence shows conflicting signals—GLP-1/GIP-1 RAs appear to reduce prostate and colorectal cancer risk but may increase thyroid cancer risk—and the biological mechanisms driving these associations are unknown. Research should elucidate how incretin mimetics modulate immune function, inflammation, metabolic signaling, hormonal pathways, or gut microbiota composition to influence cancer development, using preclinical cancer models and/or human cohort studies with documented cancer outcomes.
At-a-Glance
- Who can apply: Investigators at eligible institutions; clinical trials not permitted under this mechanism (see companion R01 PAR-25-069 for well-developed projects).
- Funding & project length: Not stated; standard R21 amounts apply (consult NIH ASSIST or Application Guide).
- Award mechanism: R21 Exploratory/Developmental Research Grant (pilot/exploratory projects).
- Key dates: Open January 16, 2025; rolling due dates (February 16, June 16, October 16, 2025, then 2026); earliest start December 2025–July 2027.
- Best fit for: Cancer biologists, endocrinologists, metabolic researchers, epidemiologists studying GLP-1/GIP-1 RA mechanisms in obesity-related cancers (thyroid, prostate, colon, lung) via mechanistic animal models or human biomarker/cohort designs.
Key Facts
Deadline
Thu, January 7, 2027
Posted
Mon, November 18, 2024
Award / Year (direct costs)
$225,000
Max Total
$450,000
Max Duration
2 years
Keywords
Research Areas
Gotchas (3)
Clinical trials are explicitly not allowed for this R21 mechanism
99%
Source Text
“Mechanisms that Impact Cancer Risk with Use of Incretin Mimetics (R21 Clinical Trial Not Allowed)”
Applicants proposing incretin mimetics other than GLP-1 RAs or GLP-1/GIP-1 RAs must provide justification that their agent is more effective and/or has more favorable side effects; route of administra
95%
Source Text
“Investigators wishing to study incretin mimetics other than GLP-1 RAs or GLP-1/GIP-1 RAs, such as dipeptidyl peptidase (DPP)-4 inhibitors, must justify why the agent(s) they propose to study are more effective and/or have a more favorable side effect profile than GLP-1 or GLP-1/GIP-1 RAs. Route of agent administration (oral vs. other) is, by itself, not an adequate justification.”
For human studies, a substantive proportion of otherwise healthy individuals in the cohort must subsequently develop cancer after starting the incretin mimetic
85%
Source Text
“Human studies involving individuals who will or have received GLP-1 or dual GLP-1/GIP1 RAs are also encouraged, so long as within the cohort a substantive proportion of otherwise healthy individuals after starting the incretin mimetic subsequently develop cancer.”