Next Generation Chemistry Centers for Fusion Oncoproteins (UM1 Clinical Trial Not Allowed) | RFA CA 23 037

Opportunity Information: Apply for RFA CA 23 037

The National Cancer Institute (NCI), part of the National Institutes of Health (NIH), is launching a coordinated research effort called the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network. The central idea is to speed up progress against pediatric cancers driven by fusion oncoproteins, which are abnormal proteins created when parts of two different genes fuse together. These fusions can act as powerful cancer drivers, especially in childhood solid tumors and brain tumors, yet many remain difficult to target with conventional drugs. This funding opportunity, RFA-CA-23-037, supports the creation of “Next Generation Chemistry Centers (NGC) for Fusion Oncoproteins” using the UM1 cooperative agreement mechanism, and it explicitly does not allow clinical trials under this award.

The purpose of the NGC Centers is discovery and early translational chemistry: teams are expected to run independent, innovation-driven research projects that apply advanced chemical biology and chemoproteomic approaches to fusion-driven cancers. In practical terms, NCI is looking for groups that can invent or deploy next-level methods to find, validate, and optimize small molecules that can disrupt fusion oncoproteins or the key molecular systems that fusion oncoproteins rely on. The solicitation emphasizes chemistry-forward strategies, meaning applicants should bring serious capability in areas like ligand discovery, target engagement measurement, proteome-wide profiling, structure-enabled design, covalent or proximity-based approaches, and other platform technologies that make “undruggable” or hard-to-drug fusion proteins more tractable.

A major theme is mechanistic diversity in how candidate compounds might work. Proposed compounds can aim to inhibit the activity of a fusion oncoprotein directly, interfere with critical protein-protein interactions needed for the fusion protein to function, or modulate coding and/or noncoding RNAs that are required for fusion-driven oncogenesis. The announcement also highlights selective degradation as a desired path, including inducing degradation of the fusion oncoprotein itself (for example, through targeted protein degradation concepts) or degrading other proteins that represent essential dependencies created by the fusion. In other words, applicants are not limited to classic enzyme inhibition; they can propose indirect or systems-level chemical strategies as long as the endpoint is a credible way to disable fusion-driven cancer biology.

The expected outputs span a range of maturity levels, which is important because NCI is not only looking for near-term “drug candidates.” Compounds emerging from these centers may be chemical probes and tool molecules that clarify biology and establish causality, more advanced lead compounds that are ready for further optimization toward a development candidate, or in some cases bona fide candidate-like molecules with strong potential to advance toward preclinical development. This framing gives applicants room to propose ambitious discovery work while still being held to a clear translational direction: generating usable small molecules and evidence that they can engage targets and alter fusion-driven disease mechanisms.

The program is structured as a network rather than isolated awards. Because this is a UM1 cooperative agreement, awardees should expect substantial programmatic involvement and coordination with NCI and other funded teams. Each NGC Center is required not only to execute its own proposed research, but also to participate in collaborative projects with U01 awardees and potentially other fusion oncoprotein researchers. The UM1 Centers will meet regularly with U01 grantees funded through the companion FOA focused on the “Mechanisms of Fusion-Driven Oncogenesis in Childhood Cancers,” creating a deliberate pipeline where mechanistic discoveries and chemistry-enabled targeting strategies can inform each other. This is meant to accelerate target prioritization, improve biological validation, and reduce duplicated effort across institutions.

Funding priorities are also clearly signaled. Preference will be given to applications that focus on fusion oncoproteins found in tumors with a high risk of treatment failure and where targeted therapy progress has been limited. The announcement particularly encourages projects in high-risk pediatric solid tumors and brain cancers, reflecting areas of urgent unmet need and historically fewer targeted treatment options. Competitive proposals, therefore, would typically justify the clinical and biological importance of the selected fusion(s), explain why existing approaches have stalled, and show how the proposed chemical strategy is genuinely positioned to break through those barriers.

From an administrative standpoint, this opportunity is categorized as discretionary funding and uses a cooperative agreement as the funding instrument, with an activity focus in education and health under CFDA 93.395. The listed award ceiling is $1,500,000. The original closing date was November 15, 2023, and the opportunity was created July 17, 2023. While the notice includes an “ExpectedAwards:” field, the number is not provided in the source text you supplied.

Eligibility is broad across U.S.-based organizational types, reflecting NIH’s typical inclusive applicant pool. Eligible applicants include 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 tribal governments and other tribal organizations; public housing authorities; nonprofits with or without 501(c)(3) status (outside higher education); for-profit organizations (other than small businesses); and small businesses, among others. The opportunity also explicitly highlights a range of institution types such as HBCUs, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, AANAPISISs, Alaska Native and Native Hawaiian Serving Institutions, faith-based or community-based organizations, regional organizations, and U.S. territories or possessions.

Foreign eligibility is restricted in a way that matters for planning partnerships. Non-U.S. entities (foreign organizations 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. However, foreign components as defined by the NIH Grants Policy Statement are allowed, meaning a U.S. applicant may be able to include certain foreign collaborations or performance sites if they meet NIH’s definition and justification requirements. This creates a pathway for international scientific input without allowing a foreign institution to serve as the primary awardee.

Overall, this RFA is designed to build a chemistry-driven engine inside a broader national network focused on pediatric fusion oncogene biology. The NCI is essentially investing in teams that can combine cutting-edge chemical biology, rigorous target validation, and collaborative network science to generate tangible small-molecule solutions for some of the most challenging and high-need fusion-driven childhood cancers, while staying firmly in the preclinical and discovery space (no clinical trials under this mechanism).

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Next Generation Chemistry Centers for Fusion Oncoproteins (UM1 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 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 $1,500,000.00 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 23 037

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