Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title
Acquired Resistance to Therapy Network (ARTNet; U54 Clinical Trial Not Allowed)
Activity Code

U54 Specialized Center--Cooperative Agreements

Announcement Type
New
Related Notices
  • August 18, 2021 - Notice of Pre-Application Webinar for Acquired Resistance to Therapy Network (ARTNet) and its Coordinating and Data Management Center (RFA-CA-21-052 and RFA-CA-21-053). See Notice NOT-CA-21-111.
  • RFA-CA-17-009 - Mechanisms of Cancer Drug Resistance and Sensitivity (U54)
Funding Opportunity Announcement (FOA) Number
RFA-CA-21-052
Companion Funding Opportunity
RFA-CA-21-053 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.395, 93.396
Funding Opportunity Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites interested investigators to develop and submit applications to form the Acquired Resistance to Therapy Network (ARTNet). The ARTNet FOA is a new funding opportunity that builds upon the Drug Resistance and Sensitivity Network (DRSN, RFA-CA-17-009) to focus study on the mechanistic basis of acquired resistance to cancer therapies and disease recurrence. Central to the ARTNet’s structural organization are team science approaches that iteratively bridge basic, pre-clinical, and translational research along the tumor-tumor microenvironment continuum to inform new strategies that can be better translated to overcome significant challenges in acquired resistance to cancer therapies.

Key Dates

Posted Date
August 04, 2021
Open Date (Earliest Submission Date)
October 01, 2021
Letter of Intent Due Date(s)

October 01, 2021

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 01, 2021 November 01, 2021 Not Applicable February 2022 May 2022 September 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. No late application will be accepted for this Funding Opportunity Announcement (FOA).

Expiration Date
November 02, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance toall requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review,

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.



  3. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites interested investigators to develop and submit applications to form the Acquired Resistance to Therapy Network (ARTNet). This FOA is a new funding opportunity of the Drug Resistance and Sensitivity Network (DRSN, RFA-CA-17-009). The ARTNet builds upon the foundational activities of the DRSN with a focus on the mechanistic bases of acquired resistance to cancer therapies and disease recurrence. Central to the ARTNet’s goals is to balance basic, pre-clinical, and translational research using an iterative team science structure that will enable hypothesis testing on the biological basis of resistance in clinically relevant model systems. Furthermore, another goal of ARTNet is to provide evidence along the shared tumor-tumor microenvironment (TME) continuum to inform new strategies that can be better translated into future clinical trials. It is envisioned that the projects proposed for an ARTNet center will be unified by an overarching scientific theme focused on addressing significant challenges in acquired resistance and disease recurrence that defines it. The intent of the ARTNet FOA is to support centers that will collectively represent a range of treatment modalities (e.g., chemotherapy, radiation, targeted agents, immunotherapies, combined modalities) and cancer type(s) in pursuit of addressing compelling questions and significant barriers in acquired therapy resistance research.

Background

Development of therapy resistance remains a significant challenge for most tumor types, which is linked to approximately 90% of all cancer-related relapses and mortality. Therapy resistance and ineffectiveness are known to arise from a variety of factors such as gain-of-function genetic mutations, epigenetic changes, metabolic reprogramming, upregulation of drug efflux transporters, and loss of target among numerous cellular and molecular mechanisms.

A sea change in the view of cancer holds that cancer cells within a tumor population may exist in a continuum of delimited states previously thought of as being in distinct phenotypic groups, such as dormancy, plasticity, and terminal differentiation. These cell states pose unique challenges wherein heterogeneity is a fertile ground for selection to act upon in either a stochastic or deterministic fashion, often leading to the emergence of acquired resistance to further therapeutic perturbance. Recent advances in single-cell - omics suggest that the organizational principles of clonal tumor networks are often intersected with nodes that control stemness and cell fates, pointing to the deep intersection between oncogenes, plasticity, and therapy resistance.

While precision oncology approaches are helpful for patient selection based on intrinsic tumor mutations, few strategies exist for addressing acquired therapy resistance including the availability of research models developed from resistant tumors. Furthermore, significant gaps remain in bridging basic discoveries to preclinical testing, which would, in turn, enable the translational development and adoption of therapeutic strategies to overcome resistance. Typically, clinical attention is focused on tumor-centric events/responses; however, it is evident that the TME plays a significant role in actively driving aggressiveness and therapy resistance. The TME constitutes a range of cellular, bioenergetic, and biophysical components that contribute to tumor adaptation mechanisms and behaviors leading to acquired resistance. Further mechanistic understanding of these microenvironmental influences as facilitators, drivers, or co-organizers in patient responses is a timely and important consideration for the cancer research community.

Key Requirements of the ARTNet Research Center

All proposed ARTNet centers must include the following main attributes (for additional details on the requirements, please see Section IV Application and Submission Information).

A. Overall Research Focus. Each proposed ARTNet center must articulate an overarching scientific theme that defines it. The proposed research projects must be aligned with the theme in testing hypotheses that address compelling questions in acquired resistance to cancer therapy.

B. Organizational Structure. Each ARTNet center must be organized as follows:

  1. Projects: Three synergistic and complementary research projects are required.
  • Two basic/mechanistic projects and one preclinical/translational project; or
  • One basic/mechanistic project and two preclinical/translational projects.

Refer below for examples of basic/mechanistic and preclinical/translational areas of research. Either configuration above must demonstrate a capacity for iteration between the basic/mechanistic and preclinical/translational projects within the ARTNet center.

2. Cores:

  • One administrative core to facilitate project management, communication, and dissemination of results within the broader ARTNet community, U24 ARTNet Coordinating Data and Management Center (CDMC), and the NCI.
  • One to three Shared Resource Cores to provide expertise, technologies, and services (e.g. models, biological specimens, -omics, imaging, statistics, pathology).

C. Research Team. Each ARTNet center must consist of appropriately diversified, interdisciplinary research teams with expertise spanning the basic/mechanistic to preclinical/translational spectrum consistent with the overarching theme and hypotheses to be tested. Multiple principal investigator (mPI) applications are strongly encouraged.

D. Outreach and Connectivity. Each ARTNet center will be collaboratively engaged with other ARTNet centers and the U24 CDMC to collectively operate as a network. The ARTNet center awardees’ participation within the broader network is intended to have national impact in developing new comprehensive cancer biology concepts with potential to inform therapeutic strategies and overcome acquired resistance.

Areas of Scientific Priority and Interests

Disentangling mechanisms of adaptation in both tumor and stromal cells that are the underpinnings of acquired resistance and disease recurrence is urgently needed to promote better hypothesis-driven research and accelerate the path towards the clinic. Advancements in the field will require strong integration and iteration between basic/mechanistic science and preclinical/translational projects. Applicants are strongly encouraged to develop mechanistic studies that examine processes of adaptation induced by treatment and move beyond sequencing of mutations as the basis of personalized therapeutic decision-making in cancer patients. Applications that propose research projects to holistically examine tumor, TME, and host systems as drivers and enablers of acquired resistance and responses to therapy in under-represented programmatic areas are encouraged.

Examples of basic/mechanistic projects may involve but are not limited to the following studies:

  • Examination of adaptive processes (e.g., cell state, metabolic reprogramming/reverse Warburg effect, epigenetic states, nonclassical cell death and survival pathways) induced by therapeutic interventions;
  • Role of TME, including resistance that arises due to therapy-induced impacts on stromal cells (e.g., cancer-associated fibroblasts [CAF], endothelial cells, neurons, adipocytes, etc.), extracellular matrix (ECM) architecture and/or density, and immune response;
  • Distinguish between resistance in primary vs. metastatic disease and develop corresponding model systems that account for the tumor ecosystem (including non-immune stromal cells, ECM, microbiome and immune components);
  • Effects of age, gender, and ethnicity on the mechanisms of TME-mediated therapy resistance in tumors that expand beyond the immune components;
  • Tumor cell/microenvironment heterogeneity (including therapy-induced);
  • CAF subtypes, endothelial subtypes, adipocytes, and cancer stem cell/stromal plasticity;
  • Elucidation of intra-tumoral cellular state diversity, (spatiotemporal) evolution, and their role in cancer progression and recurrence;
  • Investigation of organelle-based adaptive responses that culminate in metabolic reprogramming and altered cellular functions associated with cancer cell resistance to therapy; and
  • Role of the immune system in the context of non-immune stromal elements in driving acquired resistance to therapy.

Examples of preclinical/translational projects may involve but are not limited to the following studies:

  • Developing regimens (e.g., devising/optimizing schedule/sequencing/dosing/targeting) to anticipate and overcome acquired resistance through combined modality strategies (e.g., chemoradiation, small molecule inhibitor combinations);
  • Distinguishing the basis of patients' responses (e.g., durable responses relative to disease recurrence);
  • Testing and evaluating newly defined targets and biological effects based on underlying mechanisms (e.g., rewiring of/resistance to alternate usage of multiple cell death, DNA repair, epigenetic mechanisms, and survival pathways);
  • Exploring novel approaches to modulating classical and/or non-canonical oncogenic targets;
  • Defining the role of the microbiota in tumor responses and therapeutic outcomes;
  • Testing methodologies and technologies that could accelerate multiplexed monitoring and readouts of acquired resistance and/or response to therapies; and
  • Developing human-derived models of primary and metastatic disease to test translational hypotheses on acquired resistance in response to therapies.

Resource Cores

Each ARTNet center is also expected to have shared resource core capabilities to support, develop, and optimize models, approaches and technologies that feed into the basic, preclinical, and translational studies.

Examples of shared core supporting capabilities may include, but are not limited to:

  • Access to annotated pre- and post-therapy patient specimens from collaborative early phase clinical trial(s);
  • Collection and/or development of models of acquired therapy resistance (e.g., 3-D biomimetic systems, organoid cultures, patient-derived xenografts); and
  • Advanced computational, imaging, omics, and systems biology infrastructure to analyze therapy resistance processes across the tumor-TME continuum (e.g., longitudinal, spatial).

Non-Responsive Applications

Applications with one or more of the following attributes will be deemed non-responsive and will not be reviewed:

  • Applications that do not propose a combination of two (2) basic/mechanistic projects and one (1) preclinical/translation project structure (and vice versa);
  • Applications that do not include cores that directly support acquired resistance research and the needs for iterative basic/mechanistic and preclinical/translational aspects of all projects;
  • Applications that do not test an overarching acquired resistance hypothesis; and
  • Studies that focus solely on intrinsic mutations in cancer cells or fail to triangulate immune-oncology studies with additional non-immune stromal elements.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New
Resubmission

Resubmission of applications originally submitted in response to the RFA-CA-17-009.

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NCI intends to commit $6.6M in FY 2022 to fund up to five awards. The number of awards is contingent upon the submission of a sufficient number of meritorious applications. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets must reflect the actual needs of the proposed project but must not exceed $850,000 per year in direct costs.

Award Project Period

The total project period for an application submitted in response to this FOA may not exceed 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

There can be no overlap of investigators and senior/key personnel across separate applications from the same organization.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Ms. Kim Witherspoon
National Cancer Institute (NCI)
Telephone: 301-793-2119
Email: kw265c@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Component Component Type for Submission Page Limit Required/Optional Minimum Maximum
Overall Overall 12 Required 1 1
Admin Core Admin Core 6 Required 1 1
Core - use for each shared resource core Core 6 Required 1 3
Project - use for each Research Projects Project 12 Required 3 3
Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

  • Overall: Required
  • Administrative Core: Required
  • Resource Core: One (required) to three
  • Projects: 3 required (2 basic/mechanistic and 1 preclinical/translational or 1 basic/mechanistic and 2 preclinical/translational)
Overall Component

When preparing your application, use Component Type ‘Overall’.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall) 

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the scientific theme that defines the center. Justify the compelling scientific question/challenge(s) in acquired resistance to therapy that the center as a whole seeks to address. The Specific Aims in this section of the Research Plan should be overarching and distinct from the aims of the individual research projects.

Research Strategy: Provide an overview of the proposed ARTNet center. It is anticipated that the breadth of an ARTNet center will be comprehensive and encompass basic/mechanistic biology and preclinical/translational perspectives to test an overarching hypothesis that spans across the tumor-TME continuum. Describe the vision of the ARTNet center that will guide integration and iteration between Projects and Cores.

Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section A: ARTNet Center Framework. Describe the framework with respect to the ARTNet center design of a minimum of either: Two(2) basic/mechanistic research projects and one(1) preclinical/translational research project; or, one(1) basic/mechanistic research project and two(2) preclinical/translational research projects. Justify the rationale for the chosen framework.

Sub-section B: Center Integration and Iteration. Describe how the ARTNet center will foster integration and iteration among the research projects in line with testing the central hypothesis that defines the center. Describe how the center will demonstrate leadership in the context of driving a productive collaborative atmosphere of integration and iteration that bridges basic/mechanistic and preclinical/translational research.

Sub-section C: Research Innovation. Describe how the ARTNet center innovates in comprehensively deciphering the mechanistic underpinnings and clinical challenges of acquired resistance to therapy.

Sub-section D: Research Teams. Summarize the major collective strengths of the multidisciplinary teams in the proposed areas of research without duplicating information provided in the biosketches. Explain how the chosen expertise set represented by the respective team members (e.g. cancer biology, molecular medicine, translational science, computational biology, bioinformatics, others) will be integrated to advance the proposed research program. Describe the environments (e.g. academic or other entity) of the research team members and how they will support the mission of the proposed ARTNet center.

Sub-section E: Shared Resource Core(s). Briefly explain the need for the Shared Resource Core(s) and indicate how it will support all the research projects in the center.

Letters of Support: Include a letter of support from an institutional official endorsing the proposed ARTNet center and describing available institutional resources to support the research. Also, include letters from investigators who will serve as consultants or collaborators on the project but with no measurable efforts. Do not include letters from investigators who will have committed efforts in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan as specified in:

  • Industry collaboration guidelines and
  • The Federal Register, Vol. 76, No. 48, pages 13404-13410 (2011)
  • A Data and Resource Sharing Plan for unique materials, tools, animal models, reagents, and therapeutics, along with Intellectual Property (IP) and knowhow management should be provided only under the Overall component but it should cover all the activities proposed for the ARTNet center.
  • Overall Resource Sharing Plans should include a Genomic Data Sharing plan, and plans for sharing of unique reagents, materials, tools, and model organisms, where applicable.
  • The Data and Resource Sharing Plan should briefly describe the types of data and computational resources and unique biological resources that are expected to be generated and shared, consistent with achieving the goals of the ARTNet.
  • Data and Resource Sharing Plans are expected to describe plans for data anonymization, annotation, multimodal integration, harmonization, and transfer learning. Plans should include the development of robust statistical, artificial intelligence, and/or Machine Learning-ready datasets to facilitate accessible data formats and unique resources for sharing with the scientific community and the ARTNet CDMC.
  • Each Shared Resource is expected to support all Research Projects and the services, support, and/or resources to be provided to other Research Center components should be clearly defined. Issues to be addressed include:
    • Value of the Core services to the Research Center and Research Projects;
    • Integration between the Core and Research Projects;
    • Procedures for selecting Research Projects to use the Core, including allocating resources, cost-effectiveness, and increased efficiency; and
    • Quality control measures.

Any proposed new shared resources must not duplicate analogous resources already established in the applicant institutions. If existing cores and resources are to be used, then funding to augment such existing resources may be requested. Description of how work related to the Center will be prioritized within such a core must be provided.

Note that NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the policies and procedures for unique resources and data, software, and computational model sharing within the context of the NCI Cancer Data Ecosystem including infrastructure and resources for access of multi-modal data, elastic computation, and analysis through the Cancer Research Data Commons developed upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the SF424 (R&R) Application Guide must be followed.

Administrative Core

When preparing your application, use Component Type ‘Admin Core’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

  • Applicant Information

  • Type of Applicant (optional)

  • Descriptive Title of Applicant’s Project

  • Proposed Project Start/Ending Dates

 

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Administrative Core Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
  • An Administrative Core leader may also serve as the ARTNet contact PI.
  • A senior statistician may be included in this Core to provide statistical support for the Research Center. In the additional Senior/Key section, provide the role under 'Other Project Role Category' as 'Statistician'.

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package. The budget should account for the efforts of the Core Leader, Core Administrator, Statistician, and other Key Persons.
Leadership Effort Commitment: If the Center contact PD/PI is also an individual Project leader, the ARTNet contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person months of effort (in a 12-month calendar year). The required levels of effort may reflect an aggregate of effort for the entire ARTNet (listed here under Administrative Core) and the efforts for other ARTNet components, as applicable.

Restricted funds: The budget should include funds (15% of the overall ARTNet Center budget) for trans- or extra-ARTNet collaborative pilot projects for years 2-5. The process for solicitation and prioritization of collaborative project proposals will be developed within each ARTNet Center. The ARTNet Steering Committee will prioritize pilot project proposals across the Network and submit recommendations to the NCI for further consideration and approval. The collaborative project funds should be listed in the Other Expenses category under the heading "Restricted Funds".

Travel Funds: The budget should include travel funds for the PD(s)/PI(s) to attend the annual or biannual ARTNet Steering Committee meetings and participate in other network-related activities. NCI encourages early-career investigators to attend Network activities.
Other: It is expected that funds will be allocated to open-access publishing.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Administrative Core.

Specific Aims: Describe the goals of the Administrative Core.

Research Strategy: Address the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Administrative Core Structure. Outline the organization and function of the Administrative Core. Incorporate the plans for specific administrative activities of the Research Center including, but not limited to, progress reports, monthly meetings and teleconferences, development of a Center advisory group, travel for the PD(s)/PI(s) and team leaders to scientific meetings, and other activities. Describe the plans for coordination and communication with the ARTNet CDMC (U24) and NCI scientific staff. Finally, describe the plans for participation in the ARTNet Steering Committee and in cross-ARTNet activities.

Sub-section B. Administrative Core Leadership. Outline how the Administrative Core will coordinate management of the ARTNet Center components, shared resources, or resolve potential disputes. Describe how the Administrative Core will coordinate communication between basic/mechanistic and preclinical/clinical stakeholders.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: Resource Sharing Plans should only be provided in the Overall component of the application.

 

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Shared Resource Core

When preparing your application, use Component Type ‘Core’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Shared Resource Core)

Complete only the following fields:

  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project
  • Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Shared Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Shared Resource Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Shared Resource Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Shared Resource Core)

  • In the PD/PI section of the form, use Project Role of ‘Other’ with Category of ‘Shared Resource Core Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
  • An Administrative Core leader may also serve as the ARTNet contact PI.
  • A senior statistician may be included in this Core to provide statistical support for the Research Center. In the additional Senior/Key section, provide the role under 'Other Project Role Category' as 'Statistician'.
  • If the Center contact PD/PI is also an individual Core leader, the ARTNet contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person- month (in a 12-month calendar year) of effort.
  • For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Shared Resource Core)

Budget forms appropriate for the specific component will be included in the application package.

The Shared Resource Core Lead(s) must each commit and maintain through the life of the award a minimum of 0.6 person- month per year of effort (in a 12-month calendar year). If there are multiple co-leads, it is not necessary that each commit equal effort to the project.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Shared Resource Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Shared Resource Core.

Specific Aims: In addition to outlining the specific aims of the Shared Resource Core, list which projects will be supported by the Shared Resource Core.

Research Strategy: The Shared Resource Core may be physical or virtual infrastructures providing a biological, pathological, imaging, computational, or engineering resource that supports other Center components in their activities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: Resource Sharing Plans should only be provided in the Overall component of the application.

 

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Shared Resource Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Research projects

When preparing your application, use Component Type ‘Project’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project
  • Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
  • For projects with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other(Specify)' and designate the role under 'Other Project Role Category' as "Project Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Project Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

The Project Lead must dedicate 1.8 person months of effort (in a 12-month calendar year) to the project for the life of the award. If the project has multiple leads, then each lead must dedicate at least 1.2 person months of effort (in a 12-month calendar year) to the project for the life of the award.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Research Projects.

Specific Aims: Describe the goals of the proposed research project.

Research Strategy: Applicants should use the standard structure of the Research Strategy section (i.e sub-sections Significance, Innovation, Approach). Within these sub-sections, address the following additional aspects of each project:

  • Describe what basic/mechanistic or preclinical/translational challenge in acquired resistance is being addressed by each respective project across the tumor-tumor microenvironment continuum;
  • Clearly state the hypothesis for each individual research project, and describe its relationship (integration and iteration) to other proposed research projects within the ARTNet site, and the overall theme of ARTNet site as a whole; and
  • If the research project will use the Shared Resource Core, describe how the Core capabilities support the proposed project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Projects)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

The emphasis of this FOA is on highly meritorious research efforts to study the mechanistic basis of acquired resistance to cancer therapies and disease recurrence using hypothesis-driven team science approaches that would iteratively bridge basic, pre-clinical, and translational research along the tumor-TME continuum to inform new strategies that can be better translated to overcome significant challenges in acquired resistance to cancer therapies.

Scoring. Reviewers will provide an overall impact score for the entire ARTNet center (Overall). In addition, assigned reviewers will provide individual "criterion scores" for the Overall application but not for the other components.

Other components of the ARTNet application (i.e., Administrative Core, each individual Research Project, and Shared Resource Core[s]) will be evaluated but each will receive only one overall adjectival (not numerical) rating.

Overall Impact - Overall

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria - Overall

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: What is the potential for wider adoption of the technical or conceptual innovation developed by the ARTNet center to foster a comprehensive understanding of how the tumor-TME continuum contributes to acquired resistance to therapy in the long term? How adequate are the results generated by the ARTNet center to have the potential to inform basic research, clinical trial design, and/or patient outcomes?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA: How well does the ARTNet center combine/integrate expertise across basic, pre-clinical, and clinical areas of investigation? How well-recognized is the applicant PD(s)/PI(s) as leaders in their respective fields with experience in managing multidisciplinary and integrative team science?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific for this FOA: How well does the proposed ARTNet center uniquely innovate in ways to integrate-iterate across the basic/mechanistic and preclinical/translational cancer research spectrum?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA: How well does the design of the proposed ARTNet center involve hypothesis-driven approaches that bridge basic/mechanistic and preclinical/translational approaches to address acquired resistance in the tumor-TME continuum?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: How well does the scientific environment at the participating sites stimulate trans-disciplinary research collaborations? How well does the environment facilitate multidisciplinary relationships and the iterative flow between basic/mechanistic and preclinical/translational researchers?

Additional Review Criteria - Overall

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Overall

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Review Criteria for Administrative Core

Reviewers will provide only one overall adjectival impact score for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining the scientific and technical merit of the application:

As described for the Administrative Core, is there adequate evidence for the managerial and collaborative capabilities of the proposed leadership? How appropriate is the leadership structure and activities of the proposed Administrative Core in terms of facilitating: (a) achievement of the overall goals of the Research Center; (b) integration across the Research Projects and Core(s) participating in the Research Center; and (c) collaboration in cross-ARTNet activities?

Review Criteria for Shared Resource Core

Reviewers will provide only one overall adjectival impact score for the Shared Resource Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining the scientific and technical merit of the application:

  • How well-matched is the proposed Shared Resource Core to the needs of the overall Research Center? Are the services of the Shared Resource Core essential to the goals of more than one Research Project?
  • Are the qualifications, experience, and effort commitment of the Shared Resource Core Director(s) and other key personnel adequate and appropriate for providing the proposed facilities or services?
  • Will the proposed Shared Resource Core provide cost-effective services to the Research Center, prevent duplication, and/or increase efficiency?
  • What is the overall quality level of the proposed Core services and technologies and the rigor of the processes for quality control/assurance?

Review Criteria for Research Projects

Reviewers will consider each of the review criteria outlined below to assess the scientific merit of the Research Projects but will give only one adjectival rating for the entire project (criterion scoring is not used for this component). An application does not need to be strong in all categories to be judged likely to have a major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance
Does the research project address an important problem or a critical barrier to progress in the acquired resistance field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the research project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or overall basic research and clinical applications that drive this field?

Investigator(s)
Are the Lead, collaborators, and other researchers well suited to the research project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-Lead, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility, and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the research project involves human subjects and/or NIH-defined clinical research, are the plans to address:

  1. the protection of human subjects from research risks; and
  2. inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

 

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility for the project as a whole resides with the awardees, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the following primary responsibilities:

  • Participate in the annual or biannual ARTNet Steering Committee meeting, periodic conference calls organized by the ARTNet Coordinating Center, and collaborative ARTNet activities;
  • Participate in the development of various topical scientific working groups;
  • Identify and promote opportunities for ARTNet research and coordination, including collaborative pilot projects and validation of experimental concepts and observations;
  • Identify and promote trans-ARTNet and external collaborations to advance acquired resistance to therapy basic/mechanistic-preclinical/translational research;
  • Abide by the governance of the ARTNet and all network policies and procedures agreed upon by the ARTNet Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations;
  • Report progress to the NCI Program Officials on all ARTNet research and activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by program staff members on a semi-annual basis;
  • In conjunction with the ARTNet CDMC, ensure that data are deposited in a timely manner in appropriate publicly available, controlled access databases and that models, software, and other tools and resources developed as part of this Research Center are made publicly available according to ARTNet policies and procedures; and
  • Ensure that the results of the Research Projects are published in a timely manner.

The following additional responsibilities will also apply for the PD(s)/PI(s):

  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies and consistent with any binding NCI/NIH collaborative agreements with biotechnology and pharmaceutical partners and as governed by NCI-approved Data Sharing Plans and NCI-approved review for use of biospecimens collected in association with ARTNet research.
  • Due to existing agreements with pharmaceutical/biotechnology companies for NCI CTEP sponsored investigational agents, the CDMC and the entire ARTNet will be required to enter into a research collaboration agreement with NCI that will govern Intellectual Property, the exchange of data and materials within the Network, and publications. Participating ARTNet center members are also encouraged to organize and participate in other Network meetings and workshops, organize collaborative activities, and promote Trans-Network collaborations, and organize and participate in scientific and programmatic working groups.

The CTEP Intellectual Property (IP) Option applies to all ARTNet Centers' projects, regardless of the sponsor. Inventions conceived, as defined under the United States patent law, or actually reduced to practice in the performance of the Research Project under the applicable Material Transfer Agreement (MTA) or Human Material Transfer Agreement (HMTA) shall be managed in accordance with the terms of the CTEP IP Option, which can be found at:

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion various activities of the awardees. Specific responsibilities of the NCI Project Scientist(s) will include, but will not be limited to, the following aspects:

  • Serve as NCI lead Project Scientists and voting members of the ARTNet Steering Committee;
  • Serve as a resource for ARTNet in promoting interactions with other ongoing NCI activities that may be relevant to the goals of ARTNet;
  • Assist in avoiding unwarranted duplications of effort across the ARTNet program;
  • Facilitate collaborative research efforts that involve multiple ARTNet centers;
  • Evaluate the effectiveness and facilitate Program-wide adoption of resource practices;
  • Monitor operations and conduct programmatic evaluations through site visits;
  • Make recommendations on overall project directions;
  • Make funding decisions on collaborative pilot projects supported through the ARTNet center restricted funds;
  • Reviewing the progress of activities shared among the ARTNet centers and CDMC; and
  • Participate in organizing ARTNet meetings, specialized workshops, and webinars.

Additionally, an agency program official or IC program director will be responsible for the standard scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The ARTNet Steering Committee will be the Network governing body. The ARTNet Steering Committee will consist of the following voting members:

  • The PD(s)/PI(s) of each awarded ARTNet center (or senior investigator as a proxy when applicable) will collectively have one vote;
  • The PD/PI of the CDMC will collectively have one vote; and
  • The NCI Project Scientists will collectively have one vote for the NCI.

Additional NIH/NCI program staff and other government staff may participate in ARTNet Steering Committee meetings as non-voting members. The structure is designed to allow awarded investigators and NCI staff to work together to facilitate trans-ARTNet activities based on synergistic expertise and projects.

Two PD(s)/PI(s), representing two different ARTNet centers, will be selected to serve as co-chairs of the Steering Committee on a rotating basis following award issuance. All ARTNet Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The Steering Committee may have additional non-voting members.

The ARTNet Steering Committee will meet annually or biannually at the ARTNet Steering Committee Meeting and as needed through monthly Steering Committee and cross-cutting interest group virtual meetings. The ARTNet Steering Committee will:

  • Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH/NCI Program Officials for addressing such issues;
  • Establish, as necessary, subcommittees to ensure the progress of the ARTNet centers, projects, and the network;
  • Identify infrastructure(s) at individual ARTNet centers that can be shared across the network to increase efficiency and reduce costs
  • Develop procedures for soliciting and evaluating ideas for pilot projects across the ARTNet as well as criteria for their prioritization and approval;
  • Ensure that the ARTNet centers and the CDMC take advantage of existing NCI and NIH resources and programs;
  • Participate in the development of the agenda for the annual or biannual Steering Committee meeting to present scientific progress and future plans from ARTNet investigators; and
  • Coordinate dissemination of ARTNet output to the broader cancer research community.

Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings.Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

For preclinical/translational inquiries:
Michael G Espey, Ph.D., MT (ASCP)
National Cancer Institute (NCI)
Telephone: 240-276-7619
Email: SP@nih.gov

For basic/mechanistic inquiries:
Jeffrey Hildesheim, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6213
Email: HildesheimJ@mail.nih.gov

For preclinical/translational inquiries:
Percy Ivy, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email: ivyp@ctep.nci.nih.gov

Peer Review Contact(s)

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


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