Radiobiology of High Linear Energy Transfer (High LET) Exposure in Cancer Treatment (R01, Clinical Trial Not Allowed) | RFA CA 20 032

Opportunity Information: Apply for RFA CA 20 032

This NIH funding opportunity (RFA-CA-20-032) supports R01 research projects focused on the radiobiology of high linear energy transfer (high LET) radiation as it relates to cancer treatment, with clinical trials explicitly not allowed. The central scientific theme is relative biological effectiveness (RBE), meaning how much biological damage high LET radiation produces compared with conventional low LET radiation (such as standard X-rays or gamma rays) for the same physical dose. The FOA is looking for studies that can strengthen the scientific foundation of RBE models by linking radiation physics (how energy is deposited along particle tracks and across tissues) with radiation biology (how cells and tissues respond, repair, and ultimately survive or fail). The end goal is practical: produce knowledge that can better predict and potentially improve the therapeutic benefits of high LET modalities in oncology while clarifying risks to normal tissue.

A strong application under this announcement is expected to be genuinely multidisciplinary and balanced, rather than leaning heavily toward only physics or only biology. In practice, that means proposals should integrate quantitative characterization of the radiation field (for example, LET distributions, microdosimetry concepts, track structure, dose-averaged vs. fluence-averaged LET considerations, and spatial heterogeneity in mixed fields) with biological endpoints measured in relevant experimental systems (cells, organoids, normal tissue models, tumor models, and other appropriate platforms). The FOA emphasizes the need for a firm basis for RBE modeling, so projects that generate mechanistic and quantitative data that can be translated into or tested against predictive models are especially aligned.

The announcement highlights two main priority areas. First, it prioritizes applications that deepen understanding of the mechanisms that drive high LET effects in both tumors and normal tissues. This can include work that clarifies how dense ionization patterns influence DNA damage complexity, repair pathway engagement, chromosomal aberrations, cell death modes, immune and inflammatory signaling, microenvironmental responses (such as hypoxia and vascular changes), and late effects in normal tissues. Importantly, the FOA is not just asking whether high LET is "more effective," but why it behaves differently and under what conditions those differences matter. Second, it prioritizes characterization of high LET effects that could inform treatment strategies for cancers that do not respond well to conventional radiation or combined modality approaches. In other words, the program is interested in evidence that high LET radiation could help overcome known resistance mechanisms, and in data that could guide how such therapies might be used more strategically (for example, identifying tumor contexts where the biological advantages of high LET are most meaningful, while defining normal-tissue constraints).

From an administrative standpoint, the opportunity is a discretionary NIH grant mechanism (R01) under the broader health and education activity category, tied to CFDA 93.395. The agency is the National Institutes of Health, with an original closing date of 2020-03-19 and a listed award ceiling of $499,000. The eligibility scope is broad and includes many common applicant types such as public and private institutions of higher education, nonprofits (with and without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and multiple levels of government (state, county, city/township, special districts), as well as certain housing authorities and tribal entities. The FOA also explicitly calls out additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and even non-U.S. (foreign) organizations, signaling an intent to encourage a diverse pool of capable research teams.

Overall, this FOA is aimed at advancing the scientific and modeling framework needed to use high LET radiation more intelligently in cancer care. It seeks rigorous, mechanistically grounded, quantitatively informed studies that connect the physics of high LET energy deposition to biological outcomes in tumors and normal tissues, with a clear line of sight to improving treatment decision-making for difficult-to-treat, radiation-resistant cancers, without conducting clinical trials within the funded project.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Radiobiology of High Linear Energy Transfer (High LET) Exposure in Cancer Treatment (R01, Clinical Trial Not Allowed)" 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 2020-01-10.
• Applicants must submit their applications by 2020-03-19. (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 $499,000.00 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.

Apply for RFA CA 20 032

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