Wednesday, August 20, 2025 8/20/2025

Targeting 6-Phosphofructo-2-Kinase to increase efficacy of CDK4/6 Inhibitors

Award Number: R37CA234002
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Targeting 6-Phosphofructo-2-Kinase to increase efficacy of CDK4/6 Inhibitors - This extension request seeks to expand our understanding of CDK4/6 resistance in breast cancer, building upon the groundwork laid by the original grant. The primary focus of this proposal is to understand how altered glutamine metabolism can be exploited as a vulnerability in breast cancer that has developed resistance to CDK4/6 inhibitors. Our central hypothesis is that the aberrant metabolism of glutamine serves to sustain resistance to CDK4/6 inhibition in breast cancer. The main goal is to leverage this identified vulnerability in order to develop targeted therapies capable of eradicating drug-resistant forms of the disease. The specific aims of this extension involve a comprehensive exploration of the role of c-MYC in driving glutamine-induced resistance. This includes investigating c-MYC's role in global metabolic reprogramming, understanding the dependency of increased glutamine metabolism on c-MYC, and examining fuel dependencies following the loss of c-MYC. Additionally, the metabolic fate of glutamine in CDK4/6-resistant cells will be examined. Furthermore, the proposal aims to evaluate the therapeutic efficacy of a novel glutamine antagonist prodrug (JHU083) in patient- derived xenograft (PDX) models of palbociclib-resistant breast cancer. This extension request represents a significant and logical progression from the initial grant, introducing a pioneering evaluation of a novel glutamine antagonist prodrug to target glutamine addiction in ER+ CDK4/6-resistant breast cancer. Anticipating that our studies will yield crucial insights into overcoming drug resistance in breast cancer, we aim to contribute meaningful therapeutic options for a subset of patients currently lacking effective treatment alternatives.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $711,007 )
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	6	7/23/2025	EXTENSION WITH OR WITHOUT FUNDS	$711,007
														Subtotal = $711,007

Issue Date FY: 2024 ( Subtotal = $339,008 )
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	5	6/26/2024	NON-COMPETING CONTINUATION	$339,008
														Subtotal = $339,008

Issue Date FY: 2023 ( Subtotal = $349,713 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	4	6/20/2023	NON-COMPETING CONTINUATION	$349,713
														Subtotal = $349,713

Issue Date FY: 2022 ( Subtotal = $356,850 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	3	6/20/2022	NON-COMPETING CONTINUATION	$356,850
														Subtotal = $356,850

Issue Date FY: 2021 ( Subtotal = $356,850 )
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	2	6/15/2021	NON-COMPETING CONTINUATION	$356,850
														Subtotal = $356,850

Issue Date FY: 2020 ( Subtotal = $356,850 )
2020	2020	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cancer Treatment Research	000	1	7/9/2020	NEW	$356,850
														Subtotal = $356,850

Grand Total All Awards = $2,470,278

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Targeting 6-Phosphofructo-2-Kinase to increase efficacy of CDK4/6 Inhibitors

Award Number: R37CA234002

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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