Precision Approaches in Radiation Synthetic Combinations (PAIRS, R21 Clinical Trial Optional) | PAR 22 199

Opportunity Information: Apply for PAR 22 199

Precision Approaches in Radiation Synthetic Combinations (PAIRS, R21 Clinical Trial Optional) is a National Cancer Institute (NCI), National Institutes of Health (NIH) funding opportunity that supports research aimed at improving cancer treatment by pairing radiation therapy with targeted "synthetic" combination strategies. The core scientific focus is on finding and validating actionable synthetic vulnerabilities in tumors, meaning weaknesses that can be exploited when a tumor is exposed to radiation, so that an additional agent, pathway inhibition, genetic interaction, or other intervention can selectively increase tumor kill, overcome resistance, or widen the therapeutic window. The broader program goal is to generate radiation-synthetic combination approaches that are precise and biomarker-driven, and to move those approaches closer to practical use in precision oncology, ultimately contributing to the development of more effective anticancer treatments.

The opportunity is issued as a discretionary grant under Funding Opportunity Number PAR-22-199 and is associated with CFDA (Assistance Listing) 93.395. Although the title indicates an R21 mechanism and notes that clinical trials are optional, the posted description states that NCI will solicit R01 research projects; applicants should therefore verify the intended activity code and requirements in the full FOA text and application instructions, since the mechanism governs scope, budget structure, and expectations for preliminary data. The program is designed to fund research projects that directly investigate how radiation responses in tumors can be conditionally paired with synthetic lethal or synthetic vulnerability concepts, which often implies work spanning mechanistic biology, translational studies, therapeutic target identification, rational combination design, and development of predictive biomarkers that can guide which tumors or patients are most likely to benefit.

Eligibility is broad and includes many types of domestic and certain non-domestic organizations. Eligible applicants listed include state, county, and city/township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; Native American tribal governments (federally recognized); Native American tribal organizations (other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other entities. The FOA also explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities/foreign organizations. This breadth signals an intent to attract diverse institutional participation and multidisciplinary teams capable of tackling radiation biology, cancer genetics, therapeutic development, and translational research.

Key administrative details from the listing include an original closing date of 2025-09-07, a posted award ceiling of $275,000, and a creation date of 2022-06-14. The grant category is listed under education and health, reflecting the biomedical research and workforce/scientific capacity-building role NIH programs often play. While the expected number of awards is not provided in the excerpt, the ceiling and mechanism (R21 vs R01) will materially affect how ambitious a project can be within the allowed budget and timeframe, so prospective applicants typically align their aims to fit a focused, high-impact set of experiments that can establish feasibility, validate a synthetic interaction with radiation, and define a clear translational path.

In practical terms, a strong PAIRS application would usually propose a clear radiation-sensitizing or radiation-synthetic concept grounded in tumor biology, explain why the vulnerability is actionable (for example, targetable with a drug, biologic, or other intervention), and define how the combination will be tested and prioritized. Many projects in this space also emphasize patient-relevant models, identification of biomarkers or molecular signatures that predict response, and a strategy for moving toward clinical translation, which is consistent with the program emphasis on adoption into the precision medicine toolkit. Since clinical trials are described as optional, the program can support either preclinical/translational studies that build the evidence base for a future trial, or, depending on the FOA specifics, early-stage clinical testing if allowed and well-justified.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Precision Approaches in Radiation Synthetic Combinations (PAIRS, R21 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.395.
• This funding opportunity was created on 2022-06-14.
• Applicants must submit their applications by 2025-09-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $275,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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