Revision Applications for Mechanisms of Drug Resistance (U01 Clinical Trials Not Allowed) | RFA CA 19 050

Opportunity Information: Apply for RFA CA 19 050

Revision Applications for Mechanisms of Drug Resistance (U01 Clinical Trials Not Allowed) is a National Cancer Institute (NCI) funding opportunity tied to the Beau Biden Cancer Moonshot Initiative, which was created to speed up progress in cancer research. The focus here is not on starting brand-new projects from scratch, but on allowing investigators who already hold an active NCI-funded U01 cooperative agreement to submit a revision application that adds new research aims or shifts the project in new directions. In practical terms, this FOA is meant to help existing teams quickly build on what they have already established so they can dig deeper into why cancers become resistant to treatment and use that knowledge to guide smarter therapy strategies.

The scientific purpose centers on drug resistance and refractory disease, meaning tumors that stop responding or never respond well in the first place. The FOA emphasizes uncovering the underlying mechanisms that drive resistance, improving preclinical study design to better reflect real clinical resistance, and accelerating the development of effective single agents or combination therapies. A major theme is that resistance is not only about tumor cells themselves; it can also be shaped by the tumor microenvironment, so projects that address how the surrounding immune cells, stromal components, signaling factors, or other microenvironmental conditions contribute to treatment failure are aligned with the intent. The end goal is to generate insights and approaches that are relevant at the clinical level, even though the FOA explicitly does not support clinical trials under this mechanism.

Mechanistically, this opportunity uses the U01 cooperative agreement structure, which generally means a more collaborative relationship with NIH/NCI program staff than a standard research project grant. While the FOA details provided do not spell out the specific collaboration expectations, the U01 format typically involves substantial NIH scientific or programmatic involvement to help coordinate efforts, keep projects aligned with program goals, and support timely progress. The opportunity is categorized under Health (CFDA 93.396) and is listed as a discretionary funding program.

Eligibility is broad across U.S.-based organizations and public entities, including state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; and a wide range of nonprofit organizations (both with and without 501(c)(3) status). It also includes for-profit organizations other than small businesses as well as small businesses. The FOA also highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions.

At the same time, the opportunity draws a firm line on foreign involvement. Non-domestic (non-U.S.) entities are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined by the NIH Grants Policy Statement are not allowed. In effect, the funded work must be carried out without foreign components and under an eligible U.S.-based applicant organization.

The FOA is specifically for revision applications, meaning it is intended for projects that already have an NCI-funded U01 in place and are seeking support to add new aims that fit the drug resistance emphasis. The provided source details list an award ceiling of $250,000, suggesting that the revision budget is capped at that amount under this announcement. The original closing date shown is June 23, 2021, and the FOA was created on September 5, 2019. The activity is labeled as "U01 Clinical Trials Not Allowed," which signals that proposed work should remain in the mechanistic, translational, and preclinical space rather than interventional human studies, even if the outputs are intended to inform clinical strategies.

Overall, this grant opportunity is designed to help established NCI U01 teams quickly pivot or expand their ongoing research to tackle one of the most stubborn problems in oncology: why therapies fail over time and how to rationally design next-step treatments, including combination approaches, to overcome resistance in tumors and their supportive microenvironments without conducting clinical trials under this particular funding mechanism.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Revision Applications for Mechanisms of Drug Resistance (U01 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 2019-09-05.
• 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 19 050

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