Precision Approaches in Radiation Synthetic Combinations (PAIRS, RP1 Clinical Trial Optional)

The National Institutes of Health (NIH), under the U.S. Department of Health and Human Services, has released a forecasted funding opportunity titled "Precision Approaches in Radiation Synthetic Combinations (PAIRS, RP1 Clinical Trial Optional)" through the National Cancer Institute (NCI). This initiative reflects the agency’s commitment to advancing the frontiers of cancer treatment through the development of precise, scientifically rigorous approaches that exploit context-dependent vulnerabilities in tumors exposed to radiation therapy. PAIRS aligns with NIH priorities in precision oncology by leveraging conditional synthetic lethality to develop therapeutic combinations that enhance tumor specificity and minimize harm to normal tissues. The purpose of the PAIRS program is to support research projects that investigate and validate synthetic vulnerabilities emerging from tumor-specific adaptive responses to radiation therapy. By integrating these insights with the application of molecularly targeted agents, the program aims to produce radiation-synthetic combination strategies with high translational potential. This funding opportunity underscores a departure from early synthetic lethality efforts, which primarily focused on static genomic alterations, and instead embraces dynamic, radiation-induced vulnerabilities that can be clinically modulated. These radiation-induced responses offer new pathways to develop highly targeted, synergistic therapies. Funding under this opportunity will support both exploratory and full-scale research projects. Applicants may propose projects with performance periods up to two years for exploratory studies or up to four to five years for comprehensive research. This allows flexibility for early-stage hypothesis testing or more mature, robust research designs. The use of radiation therapy as a modifiable agent—through dose, scheduling, and spatial targeting—adds another layer of precision that applicants are expected to harness in their proposed studies. The overall goal is to optimize biological response and therapeutic index while facilitating clinical translation. The funding instrument is a discretionary grant under Assistance Listing 93.395 for Cancer Treatment Research. No cost-sharing or matching requirement is imposed for this opportunity, making it accessible to a wide range of applicants. Eligible applicants span a broad spectrum of institutions including but not limited to public and private institutions of higher education, state, local, and tribal governments (both federally recognized and otherwise), nonprofits with and without 501(c)(3) status, for-profit organizations, public housing authorities, and regional or community-based entities. Foreign institutions and U.S. territories are also eligible, reflecting the program’s inclusive and collaborative intent. While the NOFO has not yet been formally posted, the estimated release is expected on June 1, 2026, with applications due by November 11, 2026. Awards are projected to be announced by July 1, 2027, with the same date set for project start. The grant forecast provides applicants with early visibility into the opportunity, allowing ample time to prepare and refine proposals. No pre-application requirements such as Letters of Intent are specified, and no gated submission process is indicated at this time. For further inquiries, applicants are encouraged to contact the NCI PAIRS Program directly via telephone at 240-276-5703 or email at [email protected]. No downloadable PDF guidance or NOFO document is currently available. This forecast reflects a strategic investment in high-precision, radiation-synthetic therapeutic development with the potential to reshape treatment paradigms in oncology.