Key Dates

Related Announcements

• August 18, 2023 - Research Projects to Enhance Applicability of Mammalian Models for Translational Research (R01 Clinical Trial Not Allowed). See NOFO PAR-23-281.
• July 14, 2022 - NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional). See NOFO PAR-22-216.
• January 21, 2022 - Cancer Tissue Engineering Collaborative: Enabling Biomimetic Tissue-Engineered Technologies for Cancer Research (R01 Clinical Trial Optional). See NOFO PAR-22-099
• May 07, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.
• May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

Issued by

National Cancer Institute (NCI)

National Institute on Aging (NIA)

Purpose

Through this Notice of Special Interest (NOSI), the National Cancer Institute (NCI) invites applications for projects to establish new or to improve existing models that recapitulate cancer development, progression and treatment response in the context of age-related biological changes, and to apply these models in basic and translational cancer research. The “oncoaging” models established through this NOSI are expected to facilitate research into the underlying biology of aging mechanisms which modify cancer susceptibility and progression, and/or alter the trajectory of therapeutic responses. This knowledge is necessary to inform novel cancer therapies for the older population. Responsive projects will be focused on establishing and characterizing cancer models, that consider aging as a risk factor, demonstrating how  robustly they recapitulate human biology, assessing their clinical relevance, and validating their utility in mechanistic studies and/or translational research.

Background

Aging is driven by molecular and cellular changes at local and systemic levels leading to a gradual deterioration in resilience. A ge-dependent cell intrinsic changes (including cumulative DNA damage, cellular senescence, epigenetic alternations or mitochondrial dysfunction) directly drive tumorigenesis. Mounting evidence shows that the tumor microenvironment (TME) and systemic environment (e.g., systemic immunity and metabolism) also undergo dramatic changes with age creating a permissive milieu for cancer progression. As a result, cancer incidence and mortality rates increase exponentially with advancing age, peaking in the age group of 65 years and older. Improving cancer therapy in the older population requires insight into the extent to which aging biology contributes to tumor growth, progression to metastasis, and treatment response. Studies addressing these questions will rely on model systems where cancer can be studied in the context of aging biology.

There is a paucity of cancer models that can recapitulate age-related changes to serve the aforementioned area of cancer research. Many experimental models and platforms have been established and used in aging or cancer research, including naturally-aged animals, accelerated aging models, genetically engineered animal models, 3-D in vitro/ex vivo models, and patient-derived xenografts (PDX).  However, these models are not sufficient in serving cancer research due to limited availability, high cost, the time required to age animals, and highly variable co-existence of multi-morbidities. Accelerated aging models have been used extensively in studying aging biology but rarely to study cancer research, thereby requiring extensive characterizations, and testing of utility. Notably, although in vitro/ex vivo cancer models (e.g., 3-D spheroid/organoid, tumoroid-on-chip) integrated with tumor microenvironment are being developed, few of these models incorporate age-related changes of the microenvironmental constituents. Furthermore, xenograft models used in current p reclinical studies of cancer represent only young tumor cells and microenvironment and robust organ functions. Accumulating evidence supports the existence of an interactive relationship between aging biology and cancer, therefore, it is imperative to build suitable, clinically relevant preclinical aging models for cancer research to understand the mechanistic links between cancer and aging, test the safety and anti-cancer efficacy of therapeutics, and potentially  enhance the clinical outcomes for older adults with cancer.

Research Objectives

This notice intends to foster novel collaborations among researchers in aging biology, cancer biology, and cancer experimental therapeutics to incorporate age-related biological features into in vitro and/or in vivo models where the cancer of interest shows growth and/or metastasis (i.e., oncoaging-cancer models). Demonstration of the utility of these models in mechanistic and/or translational research is required.   

Research objectives of this notice include: 1) increase the availability and feasibility of oncoaging-cancer models by encouraging the establishment of new or modification of existing aging/cancer model platforms to study cancer growth, metastasis, and/or treatment response in the biological setting; 2) develop validation criteria to enhance the clinical relevance of these models and evaluate the effectiveness of the established models for the specific application(s); 3) determine the underlying mechanistic links between age-related changes and cancer progression, metastasis and resistance or response to drug treatment that may lead to novel target identification or combination strategy; and 4) assess the translational potential of therapeutic strategies in models with concomitant aged phenotypes. 

Projects responsive to this notice may include, but are not limited to:

• Develop and characterize oncoaging model(s)/model platforms recapitulating changes in aging tumor microenvironment of importance to cancer progression and/or treatment response.
• Develop and test innovative validation and credentialing strategies for different types of in vivo and in vitro pre-clinical models with aged microenvironmental systems or components.
• Cross-compare closely related human or mammalian models (e.g., PDXs, and derivative organoids, cell lines, or cell line xenografts, etc.) for their contribution to translationally reliable information for designing, testing, or outcome evaluation of chemo- or immuno- or radiation therapy.
• Develop models for studying cancer drug efficacy and/or toxicity in the context of age-related comorbidities.
• Develop mechanistic understanding of the interplay between the aging hallmarks and cancer progression, metastasis, and/or response to treatment.
• Determine the roles and clinical relevance of pathways/molecules associated with aging in cancer progression, metastasis, and/or treatment response.
• Identify and validate the efficacy and/or the safety of single agents or drug combinations in cancer models in association with age-related phenotypes.

This NOSI calls for research projects to establish cancer models integrated with age-related phenotype changes and to test their utilities in cancer translational research.

Research projects focused on topics listed below are not encouraged:

• Cancer research that uses models without consideration of the biological context of aging;
• Cancer prevention research that focuses on cancer risk.

Application and Submission Information

This notice applies to due dates on or after February 5, 2024, and subsequent receipt dates through July 31, 2027. Applicants must select the IC and associated NOFO to use for submission of an application in response to the NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that NOFO. Non-responsive applications will be withdrawn from consideration for this initiative.In addition, applicants using NIH Parent announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those NOFOs are acceptable and based on usual application-IC assignment practices.

Submit applications for this initiative using one of the following notice of funding opportunity (NOFO) or any reissues of these announcements through the expiration date of this notice.

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-CA-23-092” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Although NCI is not listed as a Participating Organization in all the NOFOs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Margaret Klauzinska, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-768-1152
Email: klauzing@mail.nih.gov

Weiwei Chen, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276 5986
Email: weiwei.chen@nih.gov

Max Guo, Ph.D.  
National Institute on Aging (NIA)
Telephone: 301-402-7747
Email: Max.Guo@nih.gov