The National Institutes of Health (NIH), through its National Cancer Institute (NCI), has issued a Notice of Funding Opportunity (NOFO) titled "Exploratory Grants in Cancer Control" (R21 Clinical Trial Optional), designated as Funding Opportunity Number PA-25-253. This funding opportunity encourages exploratory research grant applications aimed at advancing cancer control in areas like behavioral modification, screening, and understanding cancer etiology. The ultimate objective is to promote early-stage research that could have a substantial impact on cancer prevention, treatment, and survivorship through population-based studies and innovative methodologies. This funding is structured to support novel scientific concepts or methodologies that could significantly advance the field of cancer research.

The NCI emphasizes the reduction of cancer risk, incidence, and mortality, as well as the improvement of quality of life for cancer survivors. Priority areas include cancer surveillance, epidemiology, healthcare delivery, behavioral research, and survivor care. Specific areas of interest range from the development of tools for multi-omics data integration to behavioral interventions targeting cancer risk reduction, and surveillance strategies leveraging electronic medical records. The NOFO supports proposals without the need for extensive preliminary data, focusing instead on conceptual frameworks, innovation, and the potential for significant scientific contributions. The R21 grant mechanism allows for exploratory projects without the expectation of substantial background data, promoting high-risk, high-reward research initiatives.

Eligible applicants include higher education institutions, non-profit organizations, for-profit organizations, local governments, and certain foreign entities. This NOFO does not require cost-sharing and supports two application types: new submissions and resubmissions. The application process necessitates several registrations, including SAM, NCAGE (for foreign entities), UEI, eRA Commons, and Grants.gov. Once all registrations are complete, applications must be submitted electronically through NIH-approved platforms. The application due dates occur on standard NIH submission dates between February 2025 and July 2028. A letter of intent is not required but recommended to facilitate planning for application review.

The NCI anticipates awarding funds based on NIH appropriations and the number of meritorious applications received. The budget allows for a combined direct cost of up to $275,000 for the two-year project period, with a maximum of $200,000 in any single year. The maximum project period under this NOFO is two years. Award terms will be outlined in the NIH Notice of Award, with compliance to NIH grant policies as a requirement. Recipients must also follow the NIH’s Data Management and Sharing Policy and other reporting requirements, which include annual Research Performance Progress Reports (RPPR).

Applications will undergo a rigorous review process conducted by NIH's Center for Scientific Review (CSR) and other NCI review groups, where scientific merit, feasibility, and innovation will be assessed. Specific review criteria include the project’s significance, potential innovation, feasibility, the investigator's expertise, and the institutional environment. Applications will also be evaluated for their compliance with human subjects’ protections, the appropriateness of sample diversity, and other ethical considerations.

For support and inquiries related to the submission process, applicants may contact the eRA Service Desk or Grants.gov for technical assistance. Scientific and research-related inquiries can be directed to Mukesh Verma, Ph.D., at NCI, while financial or grants management questions may be addressed to Dawn Mitchum at NCI. Applicants are advised to review recently issued NIH policies, as well as all relevant NIH guidelines and the NIH Grants Policy Statement, which governs terms and conditions for awarded grants.