DCB Topics of Interest for Administrative Supplements in FY26

Cellular Metabolism and Nuclear Function

Supports projects to advance the understanding of how cellular metabolism enzymes and metabolites modulate transcription, DNA repair, DNA damage response and architecture within the nucleus. 

Mitochondrial Function and Dysfunction in Cancer Biology

Supports research to advance mechanistic understanding of how mitochondrial function and dynamics regulate metabolic mechanisms that drive tumor cell behavior and adaptation. 

Areas of interest include: 

• Mitochondrial genome instability and heteroplasmy
• Regulation of bioenergetics, redox balance, mitochondrial interactions with other organelles in metabolic plasticity and tumor cell state transitions
• Mitochondrial transfer in cancer 

Regulation of Cancer Cell Fate

Supports research to examine the molecular basis for cancer cell fate determination in stressed and non-stressed conditions, and the independent or interdependent roles of signaling, metabolic, and post-translational modifications in regulating this process.

Riboregulation of Signal Transduction, Cancer Cell Communication and Condensate Biology

Supports research to advance the mechanistic understanding of how coding and non-coding RNAs and RNA-binding proteins regulate cancer cell behavior and intercellular communication. 

Areas of interest include:

• RNA-mediated control of protein function (e.g., enzymes and transcription factors)
• RNA and RBPs as components and organizers of biomolecular condensates
• Emerging RNA modalities (e.g., glycoRNAs)

Spatially Resolved Functions of Cancer Cells

Supports studies on the use of artificial intelligence (AI) in cancer cell biology studies, as well as the integration of spatial and multimodal omics to systematically capture oncogenic programs and uncover how cellular states, interactions, and signaling programs are organized in space. This research must derive functional implications and new insights into the dynamic cellular responses that govern tumor formation. 

A key priority is early-onset cancers to uncover the origins and early trajectories of tumors in younger populations that may differ from later-onset disease.

Assessing the Immune Landscape in Early Onset Cancers

Supports studies examining immune profiles in early-onset cancers compared to older-onset cancers, and research exploring differences that may underlie poor immunotherapy outcomes in early-onset cancer patients.

Epigenetically-Mediated Tumor Immune-Evasion

Supports research investigating tumor cell state evolution (or plasticity) that promotes transcriptional programs, which lead to immune evasion via suppressing antigenicity, interferon responsiveness, and immune-cell engagement. 

Tumor-Infiltrating Clonal Hematopoiesis (TI-CH)

Supports studies addressing the impact of clonal hematopoiesis (CH) in non-hematological cancers. 

Engaging Experts and Expertise from Fields Outside Cancer Research

Promotes collaborations between cancer researchers and experts outside the cancer research field.

This may include support for the following activities:

• Bringing in a new collaborator with unique expertise to take advantage of advances in other fields (e.g., materials science, physics, mathematics, game design, etc.)
• Bringing in a patient advocate or community research advocate to bring a unique advocate perspective to the project and team 

Transdisciplinary Project Planning (P01 building)

Enables Principle Investigators (PIs) or Multiple Principle Investigators (MPIs) of research project grants to establish collaborations around an organizing theme relevant to, and within scope of, the parent award that would support developing a complementary research team addressing interdisciplinary research efforts focused on cancer research questions relevant to the DCB portfolio. 

The goal is to assist research project grantees develop multi-projects applications to accelerate progress in cancer research through synergistic team-building around a central theme in cancer biology. 

Data Integration to Identify and/or Validate Molecular Signatures

Supports projects that integrate genomic, transcriptomic, epigenomic, exposure, DNA adduct, proteomic, metabolomic, imaging, and/or clinical data to define and validate molecular signatures associated with carcinogenic exposures, tumor phenotypes, or cancer outcomes.  

Molecular signatures may include:

• Epigenomic signatures
• Mutation signatures
• Molecular signatures of exposure
• Proteomic signatures

Data Reuse and Integrative Analysis for Hypothesis Generation

Supports innovative reuse of existing datasets to generate new hypotheses, validate prior findings, and uncover previously unrecognized biological mechanisms across the cancer continuum. 

Cancer as a Systemic Disease

Supports expanding stromal/microenvironment research to broader systemic events, which may include: 

• Chronic disease-induced tissue remodeling
• Chronic disease induced effects on organ function
• Organ-to-organ communication effects on primary tumor initiation, evolution, or response to therapy 

Solving Problems in Metastasis

Supports studies that define or expand consideration of emergent events across the metastatic cascade.   

Accelerating the Dissemination and Integration of New Technologies, Methodologies and Approaches into Cancer Research

Promotes the sharing and utilization of new tools and approaches for cancer research.  

This may include support for the following activities:

• On-site training or travel for technical experts to implement a technology/method at a new site.
• Technology road shows, challenge/prize competitions or hackathons as a method of broadening awareness, use, and usefulness of existing resources/methods and resources
• Methods of disseminating emerging technologies/methods into use in a broader range of cancer research projects. 

Adopt and Adapt Alternative Models and Modeling Approaches

Promotes the addition of alternative modeling approaches (e.g., artificial intelligence (AI) and mathematical models, engineered microphysiological systems, etc.) to augment or replace the use of animals in the research project. 

This may include support for the following activities: 

• Bench-marking or validating the new approach
• Adapting the technology or method
• Adding functionality that enables the new modeling method to better mimic the complexity of the biological question under study

Development or Adaptation of Methods to Study the Dynamics of Biological Systems

Promotes the design and optimization of approaches/technologies that follow a process over time in a non-destructive way. This also supports the development and improvement of methods to systematically perturb living systems. 

Incorporate Advanced Modeling into Cancer Studies

Promotes incorporating advanced modeling approaches to improve our understanding of cancer progression, interaction with the microenvironment including the immune system, and response to therapy.

Advanced modeling approaches may include: 

• Artificial intelligence (AI)
• Mathematical models
• Microphysiological systems
• Organoids, organotypic models, tumor spheroids, or tumoroid models

New Approach Methodologies (NAMs) for Cancer Biology Studies

Supports studies where NAM-aware models can be utilized to derive human relevant mechanistic insights into tumor initiation and progression with greater accuracy and precision. 

Dissecting Tumor Heterogeneity via Transcriptional Regulatory Networks (TRNs)

Supports projects defining TRNs to dissect intratumor heterogeneity across the cancer continuum, with an emphasis on rare tumor cell populations associated with therapy resistance or metastasis. 

Studies should integrate single-cell multi-omics to identify subpopulation-specific TRNs (especially rare populations), prioritize key regulatory nodes, and validate their functional roles using perturbation approaches. Emphasis should be placed on linking TRN features to clinically relevant phenotypes such as treatment response or disease progression.

Post-Translational Modification (PTM) Codes and Crosstalk

Supports research on PTMs as modulators of multifunctional proteins underlying cell state (e.g. quiescence, senescence, dormancy, cell death) and plasticity in tumor-microenvironment adaptation and heterogeneity. 

Stromal Heterogeneity 

Supports studies focused on functional heterogeneity of understudied stromal cells and extracellular matrix components leading to tumor- promoting/restraining properties. 

Aging and Cancer

Supports research on the TME and/or tissue molecular aging drivers of early-onset cancer and early dissemination of cancer cells. 

Cell-Cell Communication Across the Tumor-TME

Supports studies that will evaluate tumor cell-stromal cell adaptive communication throughout tumor evolution and response to therapy.

Tumor - TME communication may include:

• Tunneling nanotubes (TNTs)
• Extracellular vesicles (EVs)
• Cell-fusion events

Diet and TME Reprogramming

Supports research focused on understanding the role of diet in metabolic microenvironment-led dependencies in cancer progression. 

Stromal Genetic Alterations

Supports studies focused on genetic alterations and underlying DNA Damage Response (DDR) mechanisms in stromal cells as direct or indirect drivers of tumor initiation, development, and/or progression. 

Reshaping the Microenvironment

Supports studies that investigate and characterize how and when cells, cell products, dietary elements/factors or host factors (e.g., systemic events, lifestyle factors, chronic disease, organ dysfunction, etc.) induce tissue remodeling within the primary or metastatic environment and their consequences.

TME as a Co-Organizer of Early Lesions and Tumors

Supports studies aimed at characterizing the role of the TME and/or extracellular matrix remodeling (including aging events) in primary tumor initiation, tumor cell dormancy, and recurrence. 

In addition to DCB Topics of Interest for Administrative Supplements, DCB-supported principal inves

tigators can submit applications for investigator-initiated administrative supplement projects that fit within the DCB research portfolio and are within scope of the parent award. 

 Please contact your program director if you have an idea for an investigator-initiated administrative supplement project.  

Application Due Date: 

NCI will accept and consider administrative supplement requests at any time through July 31. 

Requests received after July 31 will not be considered for funding. Investigators are strongly encouraged to apply early to be considered for FY26 funds.

Application and Submission Information

Please visit the NIH Administrative Supplement webpage for information on NIH application process.

Applications must be submitted using the NIH Administrative Supplement Parent Announcement or its subsequent reissued equivalent:

• PA-26-001 Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
• Access, prepare, and submit application forms using your chosen submission option (ASSIST, institutional system-to-system solution, Grants.gov Workspace).

All instructions in the SF424 (R&R) Application Guide and PA-26-001 must be followed, with the following additions:

Eligibility

• Only current awardees of an active NCI-funded (CA only) R01, R37, R00, P01, P30, P50, U01, UM1, UH3, U24, U54 or U19 are eligible to apply.
• The existing parent award must be active with a minimum of one year remaining on the parent award.
• The project and budget periods of the supplement must be within the currently approved project period for the existing parent award.
• The proposed project must be within the scope of the parent award.
• Administrative supplements are NOT permitted during a no-cost extension.
• If an applicant anticipates a balance of 25% or more of the current total costs for the parent grant, please contact the scientific research contact prior to applying.
• Only one supplement application per parent award will be accepted for consideration. For supplements to parent awards that include multiple program directors (PDs)/principal investigators (PIs), the supplement may be requested by any or all the PDs/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award.

Budget

• The budget should NOT exceed $100,000 in Direct Costs for the entire allowable 1-year project period of the application/award.
• The administrative supplement application budget is limited to 1 year only.
• Administrative supplements may only be used to meet increased costs that are within the scope of the approved award but were unforeseen when the new or renewal application or grant progress report for non-competing continuation support was submitted; supplements designed to meet cost increases for unanticipated expenses within the original scope of the project will not be considered.
• Publication costs and costs for travel to scientific conferences will not be supported.

Submitting Applications

• Application Due Date: NCI will accept and consider administrative supplement requests at any time through July 31. Requests received after July 31 will not be considered for funding. You are strongly encouraged to apply early to be considered for FY26 funds.
• Applicants should begin the supplement application abstract by stating under which administrative supplement topic they are applying.
• To facilitate efficient processing of the request, applicants are strongly encouraged to notify the assigned NCI program official for the parent award that a request has been submitted in response to this announcement.

Page Limits

The application must include the following sections and adhere to the following limits:

• Project Summary/Abstract: 30 lines of text
• Project Narrative: 3 sentences
• Research Strategy: 5 pages
• Biographical Sketch: Senior/Key Personnel and Significant Contributors only

Review and Selection Process

NCI will conduct administrative evaluations of applications and will support the most meritorious applications submitted for consideration, based upon availability of funds. Additionally, NCI program staff will evaluate applications using the following selection factors:

• Does the administrative supplement reasonably allow for the proposed project to be completed, given the time and budget requested?
• Are the proposed activities relevant to the parent grant and original work scope?
• Does the applicant demonstrate satisfactory progress towards achieving the aims of the parent grant, as appropriate to the current stage of the project?
• Does the proposed project for supplemental funding fill an identified gap in the scientific literature or DCB grant portfolio?
• Does the proposed work align with agency or NCI priorities?

Applicants are encouraged to discuss their application with their program director.