Funding Opportunity Number: PAR-25-069
Deadlines: February 5, 2025, March 5, 2025
Purpose
Through this notice of funding opportunity (NOFO), the National Cancer Institute (NCI) invites applications for investigator-initiated studies addressing mechanisms by which incretin mimetics, specifically glucagon-like peptide (GLP)-1 or dual GLP-1/ glucose?dependent insulinotropic polypepide (GIP)-1 receptor agonists (RAs), impact cancer risk. The focus on these agents is due to their reported effects on thyroid, prostate and other cancer risks, and the generally more favorable efficacy and side effect profile compared to other classes of incretin mimetics. In addition, this NOFO seeks to draw in talented scientists to the cancer biology field who may study incretin mimetic effects on diseases other than cancer. 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 adequate justification.
Research Objectives for this NOFO
General Areas of Research
Mechanistic questions that could be addressed include, but are not limited to:
- Is there a role for these agents in cancer risk reduction? If so, what preclinical models or early phase trials are appropriate to study the molecular mechanism(s) associated with risk?
- What are the incretin mimetic-induced changes in the immune system, metabolome, hormones, cytokines, or other signaling molecules that alter cancer risk? In what organ, tissue, or cell type do they originate? Do the changes occur prior to weight loss?
- Which cancers (or cancer subtypes, such as medullary vs. well differentiated thyroid) are impacted by these agents, either favorably or unfavorably, and if so, what are the mechanism(s)?
- Are there certain groups (gender, age, ethnicity or race) that would benefit from RAs more or less than others?
- Are there off-target effects that alter cancer risk? Are these off-target effects impacted by dose? If so, what are their mechanisms?
- Does the specific agent within the GLP-1, GIP-1, or dual agent list, influence the cancer promoting or tumor preventative impact? If so, what are the mechanism(s) driving the impact difference?
Scope of Work and Additional Guidance
The animal model and/or human studies should clearly indicate the population focus and provide a justification for that focus. It is anticipated that studies will evaluate animal models where a significant proportion of the animals develop cancer. 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. When feasible, investigators should evaluate mechanisms influenced by incretin mimetics in an animal model of cancer and evaluate potential changes in humans due to the medication.
We define “mechanism” as a biologic endpoint based on analyzed samples from an incretin mimetic animal model or from subjects who have or are planned to receive incretin mimetics. This NOFO does not support studies where an epidemiological endpoint is the primary aim of the project. The mechanism(s) to be studied should evaluate samples collected from animals or humans who have received incretin mimetics. For animal studies, a cancer endpoint is required. For human studies, a cancer biomarker endpoint(s) is(are) allowed, so long as the biomarker(s) has(have) clearly been associated with the development of cancer.
For more information, please see the opportunity webpage.