Opportunity Information: Apply for RFA DE 15 004
Apply for RFA DE 15 004
- The National Institutes of Health in the health sector is offering a public funding opportunity titled "Targeting Co dependent Molecular Pathways in Oral Cancer (U01)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121 Oral Diseases and Disorders Research.
- This funding opportunity was created on Apr 22, 2014 and posted on Apr 22, 2014.
- Applicants must submit their applications by Aug 25, 2014. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- The funding agency has allocated a total of $3,000,000.00 to eligible and selected applicants.
- Each selected applicant is eligible to receive up to $600,000.00 in funding.
- Eligible applicants include: 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 Private institutions of higher education Native American tribal governments (Federally recognized) Small businesses Special district governments Independent school districts City or township governments Others (see text field entitled Additional Information on Eligibility for clarification) For profit organizations other than small businesses State governments Public and State controlled institutions of higher education Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education County governments Public housing authorities/Indian housing authorities.
- Other Eligible Applicants include the following Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISISs) Eligible Agencies of the Federal Government Faith based or Community based Organizations Hispanic serving Institutions Historically Black Colleges and Universities (HBCUs) Indian/Native American Tribal Governments (Other than Federally Recognized) Non domestic (non U.S.) Entities (Foreign Organizations) Regional Organizations Tribally Controlled Colleges and Universities (TCCUs) U.S. Territory or Possession Non domestic (non U.S.) Entities (Foreign Institutions) are eligible to apply. Non domestic (non U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
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Opportunity Summary:
Targeting Co-dependent Molecular Pathways in Oral Cancer (U01) is a National Institutes of Health funding opportunity (RFA-DE-15-004) built around a practical problem in oral cancer: many tumors do not rely on a single genetic change or one dominant pathway, so therapies aimed at one target often fail as cancer cells reroute signaling or activate backup survival programs. This FOA is designed to push projects that take advantage of newly identified genomic abnormalities in oral cancer, along with the related gene and protein expression patterns observed in human tumor samples, to map out which pathways oral cancer cells truly depend on to survive and proliferate. The central scientific deliverable is the identification of co-dependent pathways, meaning pairs or networks of molecular processes that function together to keep the cancer alive, and then using that knowledge to justify combination-based targeting strategies rather than one-drug, one-target approaches.
The program emphasizes a systematic, data-driven approach that starts with real human oral cancer genomics and expression profiles and uses those datasets as a launching point for prioritizing targets. Applicants are expected to connect the dots between genomic alterations (such as recurrent mutations, copy number changes, and other abnormalities) and downstream biological consequences in signaling, transcriptional programs, protein activity, and cellular phenotypes tied to growth and survival. A key theme is moving beyond a descriptive catalog of alterations and instead determining functional dependencies: which alterations actually matter, which pathways become essential because of those alterations, and which combinations of pathway perturbations produce the strongest anti-tumor effects in credible model systems.
This is a cooperative agreement (U01), not a standard investigator-initiated grant mechanism. In practical terms, that means the funding agency anticipates a more active role in project oversight and coordination than with typical research project grants. The FOA explicitly calls for multi-disciplinary collaboration and frames the work as concept-to-proof-of-concept target exploration, rather than late-stage drug development. The expected arc is that teams will generate convincing mechanistic and functional evidence for co-dependencies and provide a rationale for combination therapy strategies that could be advanced later into translational development.
The FOA is tailored to research teams that can integrate complementary expertise. It specifically highlights the need for cancer biologists who can interpret and test tumor biology, computational biologists who can mine and integrate complex genomic and expression datasets, and specialists in model systems and/or screening assays who can rapidly and rigorously test hypotheses. The intent is to avoid siloed projects where genomic analysis is disconnected from functional validation. Instead, the funding opportunity encourages an iterative loop: computational discovery of candidate dependencies, experimental validation in relevant oral cancer models, and refinement of the pathway map to identify the most actionable combination targets.
From an administrative standpoint, the opportunity falls under the Health activity category and is associated with CFDA number 93.121 (Oral Diseases and Disorders Research). The FOA was posted on April 22, 2014, with an original and final closing date of August 25, 2014, and an archive date of September 25, 2014. The estimated total funding amount listed is $3,000,000, with an award ceiling of $600,000, and there is no cost sharing or matching requirement. While the timeline indicates this particular announcement is archived, the summary details remain useful as a blueprint for what NIH sought to fund in this topic area: integrated teams using genomics-guided strategies to uncover and validate combination-therapy vulnerabilities in oral cancer.
Eligibility is broad and includes many types of domestic U.S. organizations, such as public and private institutions of higher education, nonprofits with and without 501(c)(3) status, for-profit organizations (including small businesses), and various levels of government (state, county, city/township, special district governments, independent school districts, and public housing authorities/Indian housing authorities). The FOA also allows tribal governments and tribal organizations, and it explicitly includes a range of special designations and mission-driven institutions such as HBCUs, Hispanic-serving institutions, AANAPISIs, tribally controlled colleges and universities, Alaska Native and Native Hawaiian-serving institutions, and faith-based or community-based organizations. Importantly, non-U.S. entities are eligible as well: foreign organizations and foreign institutions can apply, non-domestic components of U.S. organizations are eligible, and foreign components are allowed as defined by NIH policy. This reflects an interest in drawing from the strongest global expertise and the most suitable patient-derived datasets and model resources, as long as the proposed work aligns with NIH requirements.
In terms of what a competitive project would look like under this FOA, the emphasis is on the target identification and exploration phase with proof-of-concept evidence, rather than on delivering a finished therapeutic product. Strong applications would likely propose a clear strategy for selecting candidate co-dependencies grounded in human tumor data, specifying how candidates will be prioritized (for example, based on recurrence, pathway convergence, association with clinical features, or synthetic lethal relationships), and then describing how those hypotheses will be tested experimentally. The most aligned projects would also demonstrate that the team can measure meaningful outputs (survival, proliferation, pathway activity, resistance mechanisms), use model systems appropriate for oral cancer biology, and generate actionable insights about which pathway combinations are most promising for therapeutic intervention.
The official announcement is hosted by NIH at http://grants.nih.gov/grants/guide/rfa-files/RFA-DE-15-004.html, and NIH provided contact pathways through the NIH Office of Extramural Research webmaster for access or technical linking issues.
Frequently Asked Questions (FAQs)
What is the "Targeting Co-dependent Molecular Pathways in Oral Cancer (U01)" funding opportunity?
It is a National Institutes of Health (NIH) funding opportunity announcement (FOA) focused on oral cancer research that aims to identify and validate co-dependent molecular pathways that oral tumors rely on to survive and proliferate. The FOA number is RFA-DE-15-004, and the activity mechanism is a cooperative agreement (U01).
What problem in oral cancer is this FOA trying to solve?
The FOA is built around the practical challenge that many oral cancers do not depend on a single genetic change or one dominant signaling route. As a result, single-target therapies often fail when cancer cells reroute signaling or activate backup survival programs. This program encourages approaches that uncover the paired or networked dependencies that keep tumors alive, supporting combination-based targeting strategies.
What does "co-dependent pathways" mean in the context of this FOA?
In this FOA, co-dependent pathways refer to pairs or networks of molecular processes that function together to sustain oral cancer cell survival and growth. The scientific goal is to identify these cooperative dependencies and use them to justify rational combination targeting strategies rather than a one-drug, one-target approach.
What is the central scientific deliverable expected from funded projects?
The central deliverable is the identification of co-dependent pathways in oral cancer and the generation of mechanistic and functional evidence showing which combinations of pathway perturbations produce strong anti-tumor effects in credible oral cancer model systems.
How does this FOA expect applicants to use human tumor data?
The program emphasizes a systematic, data-driven workflow that starts with genomic abnormalities and gene/protein expression patterns observed in real human oral cancer samples. These datasets are meant to drive target prioritization and to connect genomic alterations (for example, recurrent mutations or copy number changes) to downstream consequences in signaling, transcriptional programs, protein activity, and cellular phenotypes tied to growth and survival.
Is this FOA focused on describing genomic alterations or on proving what they do?
The FOA explicitly pushes projects beyond descriptive catalogs of alterations. Applicants are expected to determine functional dependencies: which alterations actually matter, which pathways become essential because of those alterations, and which combinations of pathway perturbations have the strongest effects in relevant models.
What kind of approach is encouraged for identifying candidate targets?
A systematic, genomics-guided approach is emphasized, where computational discovery and integration of genomic and expression datasets feed into experimental testing in oral cancer models, followed by refinement of the pathway dependency map. The FOA favors an iterative loop rather than siloed work where data analysis is disconnected from functional validation.
What does the FOA mean by "combination-based targeting strategies"?
It refers to therapeutic concepts that target more than one pathway or process at once, based on evidence that oral cancer cells depend on multiple coordinated survival and proliferation mechanisms. The FOA is intended to build a rationale for such combinations using mechanistic and functional evidence.
Is this a standard NIH research grant or something different?
It is a cooperative agreement (U01), not a standard investigator-initiated research project grant. This mechanism indicates NIH anticipates a more active role in oversight and coordination than is typical for standard research grants.
What kind of project stage is this FOA designed to support?
The FOA frames the work as concept-to-proof-of-concept target exploration. It emphasizes discovery, mapping, and functional validation of co-dependencies rather than late-stage drug development or delivery of a finished therapeutic product.
What types of expertise does the FOA say are important for a strong team?
The FOA highlights multi-disciplinary collaboration and specifically points to the value of integrating: cancer biology (to interpret and test tumor biology), computational biology (to mine and integrate complex genomic and expression data), and expertise in model systems and/or screening assays (to test hypotheses rapidly and rigorously).
Why does the FOA emphasize collaboration and integration?
The intent is to avoid disconnected, siloed projects where genomic analysis is not linked to functional validation. The FOA encourages an integrated workflow where computational target identification is directly tied to experimental validation and refinement of actionable pathway maps.
What kinds of genomic alterations are within scope for connecting to functional dependencies?
The FOA references recurrent mutations, copy number changes, and other genomic abnormalities, and expects applicants to connect these alterations to downstream signaling, transcriptional programs, protein activity, and cellular phenotypes tied to survival and proliferation.
What kinds of experimental outputs or endpoints are implied as important?
Based on the FOA description, aligned projects would measure meaningful outputs tied to tumor biology, including survival, proliferation, pathway activity, and resistance mechanisms, in model systems appropriate for oral cancer.
What does the FOA consider a competitive application strategy for prioritizing candidate co-dependencies?
The FOA indicates strong applications would propose a clear strategy grounded in human tumor data and explain how candidates will be prioritized, such as by recurrence, pathway convergence, association with clinical features, or synthetic lethal relationships, followed by experimental testing for proof-of-concept evidence.
What is the funding amount associated with this opportunity?
The estimated total funding amount listed is $3,000,000, and the award ceiling is $600,000.
Is there any cost sharing or matching requirement?
No. The FOA states there is no cost sharing or matching requirement.
What activity category and CFDA number are associated with this FOA?
The opportunity falls under the Health activity category and is associated with CFDA 93.121 (Oral Diseases and Disorders Research).
When was this FOA posted, and what were the key dates?
The FOA was posted on April 22, 2014. The original and final closing date was August 25, 2014, and the archive date was September 25, 2014.
Is this funding opportunity still open?
No. The dates provided indicate the announcement is archived, with a final closing date of August 25, 2014, and an archive date of September 25, 2014. The summary can still serve as a blueprint for the type of work NIH sought to fund in this area.
Who is eligible to apply?
Eligibility is broad and includes many types of U.S. domestic organizations such as public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (including small businesses), and government entities (state, county, city/township, special district governments, independent school districts, and public housing authorities/Indian housing authorities). Tribal governments and tribal organizations are also included.
Are mission-driven and special designation institutions included in eligibility?
Yes. The FOA explicitly includes a range of institution types such as HBCUs, Hispanic-serving institutions, AANAPISIs, tribally controlled colleges and universities, Alaska Native and Native Hawaiian-serving institutions, and faith-based or community-based organizations.
Can non-U.S. organizations apply?
Yes. The FOA states that foreign organizations and foreign institutions are eligible to apply, non-domestic components of U.S. organizations are eligible, and foreign components are allowed as defined by NIH policy.
Where can applicants find the official NIH announcement?
The official announcement is hosted by NIH at: http://grants.nih.gov/grants/guide/rfa-files/RFA-DE-15-004.html.
Who is listed as a contact for access or technical linking issues?
NIH provided contact pathways through the NIH Office of Extramural Research webmaster for access or technical linking issues.
Does the FOA aim to fund late-stage therapeutic development?
No. The FOA describes the work as concept-to-proof-of-concept target exploration and emphasizes generating a rationale for combination therapy strategies that could be advanced later, rather than delivering a finished therapeutic product within the project period.
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