Mechanisms of Fusion-Driven Oncogenesis in Childhood Cancers (U01 Clinical Trial Not Allowed) | RFA CA 23 036

Opportunity Information: Apply for RFA CA 23 036

The National Cancer Institute (NCI), part of the National Institutes of Health, is launching a coordinated research effort called the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network. This funding opportunity, RFA-CA-23-036, uses the U01 cooperative agreement mechanism and is intended to support research that explains how fusion oncoproteins actually drive cancer in children. The emphasis is on basic and mechanistic cancer biology that can reveal actionable vulnerabilities, rather than on running clinical trials (clinical trials are explicitly not allowed under this announcement). The broader purpose is to generate the kind of detailed molecular understanding that can be paired with modern chemical and drug-discovery approaches to eventually produce more precise, less toxic therapies for pediatric cancers.

The work NCI is looking for centers on the molecular mechanisms of fusion-driven oncogenesis. Fusion oncoproteins are abnormal hybrid proteins created when pieces of two genes become joined through chromosomal rearrangements, a hallmark in many childhood cancers. Because these fusions can act as master regulators of transcription, chromatin, signaling, or protein complexes, the opportunity is aimed at projects that can map the pathways and downstream effects that make these fusions tumor-forming and tumor-sustaining. Example activities specifically highlighted include dissecting the cellular and signaling pathways activated or rewired by fusion oncoproteins; defining the composition, organization, and structure of the protein complexes that fusion oncoproteins assemble or depend on; and clarifying how noncoding RNAs (ncRNAs) and post-translational modifications (such as phosphorylation, acetylation, methylation, ubiquitination, and related mechanisms) shape fusion oncoprotein function. In practical terms, NCI wants applications that can move beyond describing that a fusion exists and instead pin down the critical dependencies, interacting partners, regulatory steps, and molecular choke points that could serve as drug targets.

A key programmatic priority is impact on the hardest pediatric cancers. Funding preference is given to applications focused on fusion oncoproteins present in tumors with a high risk of treatment failure, especially where there has been limited progress in identifying targeted agents. While the scope covers childhood cancers broadly, NCI particularly encourages applications addressing pediatric solid tumors and pediatric brain tumors, areas where fusion-driven disease biology is common and where therapeutic options can be especially limited or toxic.

Because this is a U01 cooperative agreement, awardees should expect substantial program coordination and a team-science environment rather than a completely investigator-driven, stand-alone grant. U01 recipients will participate in regular interactions with UM1 grantees funded through the related “Next Generation Chemistry Centers for Fusion Oncoproteins” program. The intent is to connect deep mechanistic biology (what the fusion does, what it needs, how it can be disrupted) with advanced chemical biology and drug discovery capabilities (how to create molecules or strategies that can target those vulnerabilities). This setup signals that successful projects should be designed with collaboration and data-sharing in mind, and should produce outputs that can be translated into tractable therapeutic hypotheses for downstream development.

Eligibility is broad and includes many U.S.-based organization types across academia, government, nonprofits, and industry. Eligible applicants include state, county, city/township, and 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; Native American tribal organizations (including those other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (outside of higher education); for-profit organizations other than small businesses; and small businesses. The announcement also explicitly calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, 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, it draws clear boundaries on foreign participation: non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply, but “foreign components” (as defined by NIH policy) are allowed, meaning certain project activities can be performed abroad when appropriately justified and compliant with NIH rules.

From an administrative standpoint, the opportunity is listed under CFDA 93.396 and falls under the broad activity area of education/health, consistent with NCI research funding. The original application due date was November 15, 2023, and the listed award ceiling is $325,000. Overall, this announcement is essentially a call for rigorous, mechanism-first research on pediatric fusion oncoproteins that can expose concrete therapeutic entry points, conducted within a coordinated network that links biological discovery to next-generation chemistry and targeting strategies.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Mechanisms of Fusion-Driven Oncogenesis in Childhood Cancers (U01 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): 93.396.
• This funding opportunity was created on 2023-07-17.
• Applicants must submit their applications by 2023-11-15. (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 $325,000.00 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 23 036

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