Key Dates

PAR-21-331: Mechanisms that Impact Cancer Risk After Bariatric Surgery (R01 Clinical Trial Optional)

PAR-21-332: Mechanisms that Impact Cancer Risk After Bariatric Surgery (R21 Clinical Trial Not Allowed)

NOT-CA-22-106: Notice of Intent to Publish a Funding Opportunity Announcement for Mechanistic links between diet, lipid metabolism, and tumor growth and progression (R01 Clinical Trial Not Allowed)

National Cancer Institute (NCI)

The National Cancer Institute (NCI) intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) with special receipt, referral, and/or review conditions (PARs) inviting R21 applications for Research Projects that identify and define the mechanisms that link diet with lipid metabolism-mediated tumor growth and progression.

This proposed funding announcement has three goals: one, to support fundamental studies designed to identify and define the molecular mechanisms through which lipid metabolism mediates tumor growth and progression, focusing specifically on the central role lipids play in linking diet with the biology of cancer; two, bridge the historically divided fields of nutrition and molecular metabolism; and three, stimulate research and tool development in this emerging area, which faces particular challenges because of the complexity of lipid biochemistry.

This Notice of Intent to Publish (NOITP) is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. To ensure appropriate expertise in nutrition, all applicants are encouraged to include a co-Investigator or use an MPI structure; applications that fail to include appropriate expertise in nutrition and/or do not propose fundamental, mechanistic investigations will be considered non-responsive. Furthermore, applications that include collaborators from fields outside of cancer research are particularly encouraged. The FOA is expected to be published in Late Summer 2022 with an anticipated application due date in Fall 2022.

This Notice encourages investigators with expertise and insights into this area of fundamental cancer metabolism to begin to consider their applicatinos to this new FOA. Collaborative investigations combining expertise in cancer metabolism and nutrition will be encouraged, and these investigators should also begin considering applying to this program. Among the areas of research encouraged in this initiative are nutrition, metabolism, metabolomics, lipidomics, genomics, genetics, glycobiology, cell biology, biochemistry, systems biology, and mathematical models examining the mechanisms that link dietary nutrients to pathways of lipid metabolism that influence tumor growth and progression.

There is broad interest in the relationship between diet and tumor growth and progression, and although additional studies are needed, the dietary patterns of patients have been reported to influence cancer outcomes. Dietary composition is known to influence the availability of metabolites at all levels, from organs to cells, but there is insufficient data detailing how differences in nutrient intake manifest at a mechanistic level. Molecular metabolism, especially lipid metabolism, is an important mediator of these effects. These FOAs, which align with Goal 4 of the recent NIH Strategic Plan for Nutrition Research, will help address the hurdles facing this promising area of investigation. Fundamental knowledge of how different diets directly and indirectly impact tumor growth and progression will aid in the generation of improved dietary guidelines that optimally support standard therapeutic approaches.

Examples of responsive research questions include, but are not limited to:

• How do known driver mutations such as p53, KRAS, and MYC influence lipid metabolism in tumor cells in response to diet?
• What are the molecular mechanisms that moderate the differential effects of different biochemical species of dietary lipids, such as palmitate and linoleic acid, on tumor progression?
• How do diet-driven variations in the level and/or composition of fatty acids in serum or tumor interstitial fluid impact any or all of the following molecular processes in tumor and stromal cells?
  • lipid-mediated signaling
  • de novo lipogenesis
  • mitochondrial function
  • the production of reactive oxygen species
• How are alterations in diet-responsive lipid metabolism in tumors buffered or enhanced by the tumor microenvironment?
• What are the molecular mechanisms through which diet-responsive circulating factors such as adipokines and steroid hormones influence cancer cell metabolism and tumor progression
• How does dietary composition affect lipid metabolism in tumors and the tumor microenvironment in the absence of weight gain?

The PAR will be open to all qualified applicants, including new and early-stage investigators, who can establish and lead a multi-disciplinary research project to enable the fulfillment of the intended program goals. Applications that examine how any of the above topics contribute to health disparities are welcome and encouraged. It should also be noted that to facilitate the entry of new investigators, especially new clinical investigators, into the field, preliminary data will be limited; applications including unpublished data more than one-half page or more than one figure will be considered noncompliant with the FOA instructions and will not go forward to review.

More details will be outlined in the forthcoming FOA.

Applications are not being solicited at this time. 

Please direct all inquiries to:

Kristine Willis, Ph.D.

National Cancer Institute (NCI)

301-792-1338

Email: [email protected]

Natalia Mercer, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6220
Email: [email protected]