Revision Applications for Mechanisms of Drug Resistance (U54 Clinical Trials Not Allowed) | RFA CA 19 051

Opportunity Information: Apply for RFA CA 19 051

The grant opportunity "Revision Applications for Mechanisms of Drug Resistance (U54 Clinical Trials Not Allowed)" (RFA-CA-19-051) is a National Institutes of Health (NIH), National Cancer Institute (NCI) funding announcement tied to the Beau Biden Cancer Moonshot initiative, which focuses on speeding up progress in cancer research. This particular FOA is not for brand-new center awards; it is specifically designed to fund revision applications (often called competitive revisions) to existing, already-funded NCI Specialized Center Cooperative Agreements under the U54 mechanism. In practical terms, the goal is to let currently supported NCI centers add new research aims or shift into new directions that strengthen the center's ability to address one of cancer treatment's biggest hurdles: how and why tumors become resistant to therapy, and what can be done about it.

The scientific emphasis is on mechanisms of drug resistance and on generating information that can translate toward clinical impact, without actually running clinical trials under this award. The FOA prioritizes work that explains the underlying biology of resistance (for example, tumor-intrinsic changes, pathway rewiring, genetic or epigenetic adaptation, phenotypic switching, and similar processes), as well as resistance driven or supported by the tumor microenvironment (such as immune context, stromal interactions, hypoxia, vascular factors, or other extrinsic pressures). Alongside discovering and characterizing these mechanisms, the announcement highlights preclinical design, meaning it encourages rigorous model development and testing strategies that better predict clinical outcomes. A major intended outcome is to foster development of single-agent or combination approaches that can effectively target resistant or refractory tumors and/or the microenvironmental factors that allow resistance to emerge or persist. Even though the work is meant to inform the clinic, the FOA explicitly indicates "Clinical Trials Not Allowed," so the supported activities must remain in the preclinical and translational space rather than interventional human studies.

From an administrative standpoint, this is a discretionary grant program using a cooperative agreement funding instrument. A cooperative agreement (U54) typically means NIH/NCI expects substantial involvement in the project, such as shared steering, coordination, or programmatic input beyond what is typical for a standard research project grant. The activity category is listed under Education and Health, and the CFDA number associated with this program is 93.396, which corresponds to NCI research support.

Eligibility is broad across many organization types, but it is constrained by the fact that it supports revisions to currently funded NCI Specialized Center cooperative agreements. Eligible applicant organizations include a wide range of domestic entities such as state, county, and local governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; special district governments; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The FOA also explicitly calls out additional categories of eligible applicants, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), 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, and U.S. territories or possessions.

Foreign participation is handled in a nuanced way. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as the applicant organization, and non-domestic components of U.S. organizations are also not eligible to apply as components. However, "foreign components" are allowed as defined by the NIH Grants Policy Statement, meaning a U.S. applicant may include certain foreign collaborations or elements if they meet NIH's definition and are justified and compliant with policy. This structure is common in NIH funding when the primary awardee must be U.S.-based but specific international scientific contributions can still be included under defined conditions.

Key logistics included in the source data are that the agency is NIH, the original closing date was June 23, 2021, and the award ceiling listed is $250,000. The record does not specify the exact number of expected awards in the provided excerpt. The opportunity was created on September 6, 2019. Overall, the FOA is aimed at accelerating meaningful progress against therapy resistance by enabling existing NCI U54 centers to expand into new, strategically chosen research aims that clarify resistance biology and strengthen preclinical-to-clinic translation, while keeping the work outside the scope of clinical trials.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Revision Applications for Mechanisms of Drug Resistance (U54 Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.396.
• This funding opportunity was created on 2019-09-06.
• Applicants must submit their applications by 2021-06-23. (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 $250,000.00 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 19 051

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