The National Cancer Institute (NCI), a part of the National Institutes of Health (NIH), has issued a Funding Opportunity Announcement (FOA) for R21 exploratory/developmental research projects under the "Precision Approaches in Radiation Synthetic Combinations" (PAIRS) program. This program focuses on identifying synthetic vulnerabilities that emerge when tumors respond to radiation therapy, and pairing them with targeted treatments to enhance the effectiveness of cancer therapies. Researchers are encouraged to develop and test novel radiation-synthetic combinations, from pre-clinical work to early clinical trials, as part of a broader precision medicine strategy to improve cancer treatment outcomes.

The purpose of the PAIRS program is to support the development of innovative cancer therapies that leverage the interaction between radiation therapy and synthetic combination agents. These projects should aim to exploit the specific vulnerabilities in tumor cells that radiation therapy induces, allowing for more precise and effective cancer treatments. Research may include combinations with molecularly targeted agents and focus on various biological processes such as epigenetic reprogramming, metabolic shifts, and changes in the tumor microenvironment. Projects should align with the overarching goal of enhancing the therapeutic index—targeting cancer cells while minimizing damage to normal cells.

The funding is provided under the R21 grant mechanism, which is designed for exploratory or developmental research. The total direct costs for the two-year project period may not exceed $275,000, with no more than $200,000 requested in any single year. Applicants are encouraged to generate preliminary data that can support the feasibility of their synthetic combination strategy, providing a basis for future translational research. Applications must demonstrate how their proposed combination integrates radiation therapy and targets a specific vulnerability in cancer cells.

Eligible applicants include higher education institutions, nonprofits, small businesses, for-profit organizations, and local or state governments, among others. The program is open to domestic and foreign institutions, including non-domestic components of U.S. organizations. Multi-Principal Investigator (Multi-PI) applications are encouraged to facilitate team science efforts that integrate cancer biology, radiobiology, and targeted therapy expertise. Applications that do not integrate radiation into the synthetic combination design, or focus solely on screening molecular targets without incorporating radiation, will be considered non-responsive.

Applications must be submitted electronically through NIH's ASSIST system, Grants.gov, or institutional system-to-system platforms. Deadlines for new applications are set on a recurring basis, with the next submission date being October 16, 2023. Letters of intent are encouraged but not required, and they should be submitted 30 days before the due date. The review process will assess the significance, innovation, approach, and potential impact of the proposed research, along with the qualifications of the research team.

The earliest anticipated start date for applications submitted in October 2023 is July 2024. Interested applicants are encouraged to reach out to program contacts for guidance, especially if there are concerns about the responsiveness of their proposals. The program runs until September 8, 2025, giving ample opportunity for multiple submission attempts.

In summary, the PAIRS R21 program offers a critical opportunity for researchers to contribute to the development of new cancer therapies that combine radiation with other treatments in a precision medicine framework. Researchers from a wide range of institutions are eligible, and proposals must clearly integrate radiation into their synthetic combination strategy.