Precision Approaches in Radiation Synthetic Combinations (PAIRS, R01 Clinical Trial Optional)

The National Cancer Institute (NCI), a component of the National Institutes of Health (NIH), under the U.S. Department of Health and Human Services, has announced a funding opportunity titled "Precision Approaches in Radiation Synthetic Combinations (PAIRS, R01 Clinical Trial Optional)." This grant supports R01 research projects focused on exploring actionable synthetic vulnerabilities that emerge in tumor responses to radiation therapy. These investigations are aimed at creating and adopting new radiation-synthetic combination strategies to enhance the precision medicine toolkit for more effective cancer treatment. The PAIRS program invites research projects that integrate radiation therapy into synthetic combination strategies, capitalizing on the conditional effects radiation has on tumors. Projects may involve pre-clinical experiments through early-phase clinical trials, emphasizing designs where radiation treatment is a key component. The synthetic combinations under this program are not limited to traditional genetic interactions but can include a range of reprogramming or adaptive cancer cell processes. These include epigenetic and metabolic reprogramming, organelle-linked stress responses, RNA processing, tumor microenvironment dynamics, and more. This opportunity is open to a wide range of applicants including higher education institutions (both public and private), nonprofits, for-profit organizations, local governments, federal agencies, tribal governments and organizations, and even foreign institutions. There is no limitation on the number of applications per organization, provided each proposal is scientifically distinct. Projects must reflect a clear rationale for the selected radiation modality and targeted agents, with a foundation of preliminary data to support feasibility and translational potential. The application process requires adherence to SF424 (R&R) guidelines and must be submitted electronically through platforms like NIH ASSIST, Grants.gov Workspace, or an institutional system-to-system (S2S) solution. While letters of intent are not mandatory, they are encouraged and should be submitted 30 days prior to the application due date. Contact for letters of intent is Ms. Julie Hong at hongj@mail.nih.gov. Applicants requesting over $500,000 in direct costs in any year must contact NIH staff at least six weeks prior to submission. The FOA was originally posted on June 14, 2022, with the earliest submission date being September 5, 2022. Applications are reviewed in standard NIH cycles with due dates typically in February, June, and October. The current expiration date is May 24, 2025, per updated notice NOT-OD-25-113. Applications must be submitted by 5:00 PM local time of the applicant organization, and the program is not subject to Executive Order 12372 intergovernmental review. Evaluation criteria include significance, innovation, approach, investigator qualifications, and environment. For clinical trials, the review will consider the appropriateness of the design, statistical methods, inclusion plans for human subjects, and timelines. Administrative contacts include Dr. Pataje Prasanna for scientific inquiries (Pat.Prasanna@nih.gov), Shane Woodward for financial matters (Woodwars@mail.nih.gov), and general application support contacts through eRA Commons and Grants.gov.