Opportunity Information: Apply for PAR 14 314
Apply for PAR 14 314
- The National Institutes of Health in the education health sector is offering a public funding opportunity titled "New Approaches to Synthetic Lethality for Mutant KRas Dependent Cancers (U01)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.396 Cancer Biology Research.
- This funding opportunity was created on Aug 7, 2014 and posted on Aug 7, 2014.
- Applicants must submit their applications by Jul 8, 2015. (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 $750,000.00 in funding.
- Eligible applicants include: Others (see text field entitled Additional Information on Eligibility for clarification) City or township governments Public housing authorities/Indian housing authorities Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education Independent school districts State governments Native American tribal organizations (other than Federally recognized tribal governments) Public and State controlled institutions of higher education Private institutions of higher education Native American tribal governments (Federally recognized) Small businesses Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Special district governments County governments For profit organizations other than small businesses.
- 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:
The funding opportunity PAR 14-314, titled "New Approaches to Synthetic Lethality for Mutant KRas Dependent Cancers (U01)," is an NIH/NCI cooperative agreement designed to accelerate the discovery of druggable vulnerabilities in cancers that rely on mutant KRAS. The central idea is synthetic lethality: finding genes or pathways that, when inhibited, selectively kill KRAS-mutant, KRAS-dependent tumor cells while sparing cells that do not share that dependency. This focus reflects a long-standing challenge in oncology, where KRAS has historically been difficult to inhibit directly and where KRAS-driven signaling involves complex processing steps and interconnected effector and regulatory networks that can blunt the impact of single-target approaches.
A key emphasis of the FOA is improving how synthetic lethality targets are found. Earlier, first-generation screening efforts often produced inconsistent or hard-to-reproduce results, in part because of limitations in screening technology and because many assays were not performed in models that truly reflect tumor biology. In response, NCI is explicitly encouraging "advanced or improved approaches" that deliver better specificity (so hits are more likely to be true KRAS-dependency relationships), better reproducibility (so findings hold up across laboratories and experimental repeats), and stronger performance in physiologically relevant model systems (such as models that better mimic real tumor contexts rather than overly simplified cell line conditions). In practical terms, applicants are being pushed to propose screening strategies that can separate general essential genes from KRAS-context-specific dependencies, and to validate findings in models that increase the likelihood of clinical relevance.
This FOA is also structured to build a coordinated research network connected to the NCI Frederick National Laboratory for Cancer Research (FNLCR) RAS Program. Awardees are expected to interact closely with the FNLCR RAS Program, actively share results with other funded groups, and participate in cross-validation of targets identified across the network. That cooperative structure is a defining feature of the U01 mechanism here: it is not simply independent investigator-driven projects running in parallel, but a coordinated set of teams that exchange data and help confirm one another's discoveries, with the goal of converging more quickly on the most credible and actionable synthetic lethal targets for KRAS-dependent cancers.
Administratively, the opportunity is categorized as a discretionary program and uses the Cooperative Agreement funding instrument (U01), indicating substantial NIH programmatic involvement and collaboration expectations. It falls under the NIH/NCI umbrella with CFDA number 93.396 (Cancer Biology Research). The posted date and creation date were August 7, 2014, with an original and current closing date of July 8, 2015, and an archive date of August 8, 2015. The listed award ceiling is $750,000, and there is no cost sharing or matching requirement.
Eligibility is broad and includes many types of domestic U.S. organizations, such as public and private institutions of higher education, nonprofits (including those with and without 501(c)(3) status), small businesses, for-profit organizations (other than small businesses), and multiple levels of government entities (state, county, city/township, special district governments), as well as tribal governments and tribally controlled institutions. The FOA also explicitly allows non-U.S. participation: foreign organizations and foreign institutions are eligible to apply, non-domestic components of U.S. organizations are eligible, and foreign components are allowed under NIH policy definitions. The eligibility language also highlights inclusion of a range of institution types such as HBCUs, Hispanic-serving institutions, AANAPISIs, Alaska Native and Native Hawaiian-serving institutions, tribally controlled colleges and universities, faith-based or community-based organizations, U.S. territories or possessions, and certain eligible federal agencies.
Overall, PAR 14-314 is a targeted NCI effort to move beyond earlier, less reliable KRAS synthetic lethal screens and to generate a pipeline of well-validated KRAS-specific vulnerabilities using improved screening and model systems, while also creating an organized, collaborative network anchored by the FNLCR RAS Program to speed confirmation and prioritization of the most promising therapeutic targets.
Frequently Asked Questions (FAQs)
What is PAR 14-314?
PAR 14-314 is an NIH/NCI funding opportunity titled "New Approaches to Synthetic Lethality for Mutant KRas Dependent Cancers (U01)." It supports research to accelerate the discovery of druggable vulnerabilities in cancers that depend on mutant KRAS.
Which NIH institute is sponsoring this opportunity?
This opportunity is sponsored under NIH/NCI (National Cancer Institute).
What is the main scientific goal of this FOA?
The FOA aims to identify synthetic lethal targets for KRAS-mutant, KRAS-dependent cancers. The goal is to find genes or pathways that, when inhibited, selectively kill KRAS-dependent tumor cells while sparing cells that are not dependent on mutant KRAS.
What does "synthetic lethality" mean in the context of this FOA?
In this FOA, synthetic lethality refers to finding gene or pathway vulnerabilities where inhibition is lethal specifically in KRAS-mutant, KRAS-dependent tumor cells, but not lethal (or much less harmful) in cells that do not share that KRAS dependency.
Why is this FOA focused on KRAS-dependent cancers?
The FOA emphasizes KRAS-dependent cancers because KRAS has historically been difficult to inhibit directly, and KRAS-driven signaling involves complex processing steps and interconnected effector and regulatory networks. These complexities can reduce the effectiveness of single-target approaches, making synthetic lethal strategies especially relevant.
What types of approaches does NCI want to encourage for finding synthetic lethal targets?
NCI is explicitly encouraging advanced or improved approaches to identifying synthetic lethal targets, with an emphasis on better specificity, better reproducibility, and stronger performance in physiologically relevant model systems.
What problems in earlier synthetic lethal screening efforts is this FOA trying to address?
The FOA highlights that earlier first-generation screening efforts often produced inconsistent or hard-to-reproduce results. Contributing factors included limitations in screening technology and the use of assays and models that did not adequately reflect real tumor biology.
What does the FOA mean by improving "specificity" in screening?
Improving specificity means designing screening strategies so that identified "hits" are more likely to reflect true KRAS-dependency relationships, rather than general vulnerabilities that affect many cells regardless of KRAS context.
What does the FOA mean by improving "reproducibility"?
Improving reproducibility means that findings should hold up across laboratories and across repeated experiments, reducing the likelihood that targets are artifacts of a particular method, model, or experimental setup.
What kinds of model systems are encouraged by this FOA?
The FOA encourages the use of physiologically relevant model systems that better mimic real tumor contexts, rather than relying solely on overly simplified cell line conditions.
How does the FOA expect applicants to distinguish KRAS-specific dependencies from general essential genes?
Applicants are pushed to propose screening strategies capable of separating general essential genes (needed broadly for cell survival) from KRAS-context-specific dependencies (vulnerabilities tied specifically to KRAS-mutant, KRAS-dependent tumor biology).
What is the funding mechanism for PAR 14-314?
The funding mechanism is a Cooperative Agreement (U01), which indicates substantial NIH programmatic involvement and collaboration expectations.
What does it mean that this is a cooperative agreement (U01) rather than a standard grant?
Based on the FOA description, the U01 cooperative structure means projects are not intended to operate as fully independent efforts in isolation. Instead, funded teams are expected to coordinate, share results, and participate in cross-validation activities as part of a network, with substantial involvement and collaboration expectations tied to NIH programmatic participation.
Is this opportunity intended to create a coordinated research network?
Yes. A defining feature of the FOA is building a coordinated research network connected to the NCI Frederick National Laboratory for Cancer Research (FNLCR) RAS Program to speed confirmation and prioritization of credible targets.
What is the role of the FNLCR RAS Program in this FOA?
The FOA is anchored to the FNLCR RAS Program. Awardees are expected to interact closely with the program, share results with other funded groups, and participate in cross-validation of targets across the network.
What collaboration and sharing expectations are described in the FOA?
Awardees are expected to actively share results with other funded groups, interact closely with the FNLCR RAS Program, and participate in cross-validation of targets identified across the network.
What is meant by "cross-validation" in this networked structure?
Cross-validation refers to network participants helping confirm one another's discoveries, so that targets identified by one group can be tested and validated by others to converge more quickly on credible and actionable synthetic lethal targets.
What is the CFDA number associated with this opportunity?
The CFDA number is 93.396, listed as Cancer Biology Research.
How is this program categorized administratively?
The opportunity is categorized as a discretionary program and uses the Cooperative Agreement funding instrument (U01).
What is the award ceiling for this FOA?
The listed award ceiling is $750,000.
Is cost sharing or matching required?
No. The FOA states there is no cost sharing or matching requirement.
When was this opportunity posted?
The posted date (and creation date) is August 7, 2014.
What were the closing date and archive date?
The original and current closing date is July 8, 2015. The archive date is August 8, 2015.
Who is eligible to apply?
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); small businesses; for-profit organizations (other than small businesses); and various government entities (state, county, city/township, and special district governments), as well as tribal governments and tribally controlled institutions.
Are foreign organizations eligible to apply?
Yes. The FOA explicitly allows non-U.S. participation. Foreign organizations and foreign institutions are eligible to apply, non-domestic components of U.S. organizations are eligible, and foreign components are allowed under NIH policy definitions.
Does the FOA mention eligibility for specific institution types such as minority-serving institutions?
Yes. The eligibility language highlights inclusion of institution types such as HBCUs, Hispanic-serving institutions, AANAPISIs, Alaska Native and Native Hawaiian-serving institutions, and tribally controlled colleges and universities.
Are community-based or faith-based organizations included in eligible applicant types?
Yes. The eligibility language includes faith-based or community-based organizations.
Are U.S. territories or possessions included in the eligibility language?
Yes. The eligibility language includes U.S. territories or possessions.
What kinds of outcomes is NCI trying to achieve through this FOA?
The FOA is intended to move beyond earlier, less reliable KRAS synthetic lethal screens and generate a pipeline of well-validated KRAS-specific vulnerabilities using improved screening and model systems, while using a collaborative network to speed confirmation and prioritization of the most promising therapeutic targets.
Is the FOA more focused on discovery, validation, or both?
Based on the description provided, it is focused on both improved discovery (advanced screening approaches) and validation (use of physiologically relevant models and cross-validation across a coordinated network).
What cancer context is most relevant for the proposed work?
The FOA is focused on cancers that are KRAS-mutant and KRAS-dependent, meaning tumor cells rely on mutant KRAS for survival and growth and may be selectively vulnerable to synthetic lethal strategies.
Why does the FOA stress physiologically relevant tumor models?
Because earlier screens often relied on models that did not adequately reflect tumor biology, the FOA stresses models that better mimic real tumor contexts to increase the likelihood that identified targets are clinically relevant.
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