Wednesday, February 18, 2026 2/18/2026

Role of microbial-modulated bile acid receptor signaling in breast cancer

Award Number: R01CA253329
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Role of microbial-modulated bile acid receptor signaling in breast cancer - SUMMARY Anti-tumor immunity varies due to interactions between innate and adaptive immune cells, microbial community diversity, host and microbially derived metabolites, and other local factors that shape tumoricidal responses. While most of the recent microbiome research focuses on the gut microbiome and cancer outcomes, extra-intestinal microbial communities are detected in the tumor microenvironment (TME). We recently reported that specific microbes identified in patient breast tumors compared to pathologically normal breast samples associated with tumor stage, tumor subtype, and for the first time, race. Triple Negative Breast Cancer (TNBC), an aggressive subtype that has generally eluded personalized medicine approaches, contained unique microbes that may mediate immunosuppression and impact standard chemotherapy or immune checkpoint inhibitor (ICI) efficacies. Yet to date, mechanisms underpinning these observations are unresolved as to how the gut and/or extra-intestinal microbiome influence BC onset, progression, and response to therapies, which is a major knowledge gap in this field. One cogent mechanism that may link microbes to anti-tumor immunity are microbially modified metabolites, namely bile acids. Certain microbes rich in 7-alpha-hydroxylase convert primary to secondary bile acids which regulate bile acid composition. Bile acids have been shown to limit progression and metastasis in other cancers through reversing immunosuppression, but minimal work has explored the role of bile acids in BC. Bile acids signal through several bile acid receptors including farnesoid X receptor (FXR). We posit that specific gut or local resident microbes that impact bile acid pools and composition will interact with cells expressing FXR to regulate the TME immune milieu. We report for the first time that patients with high FXR expression have greater relapse-free survival uniquely in TNBC subtype, but not in less aggressive luminal BC subtype, suggesting potential for targeted approaches. The overall objective of this proposal is to test mechanisms linking MicrobesBile AcidsTNBC which poses an opportunity to generate novel therapeutics and precision medicine informed by microbial compositions. Our innovative approach interrogates targetable microbial pathways that we demonstrate change the microbiome, bile acids, and tumor progression. Our central hypothesis is microbial composition and microbially-modified metabolic products, such as bile acids, increase immunotherapeutic efficacy through reprogramming the TME leading to enhanced anti-tumor immunity. We will test our hypothesis by performing the following aims: 1) Determine if commensal microbes play a physiological role in TNBC anti-tumor immunity; 2) Determine if the microbiome alters immunosurveillance of early tumor onset and progression; 3) Determine if pharmacologic bile acid receptor agonism improves TNBC immunotherapy. Findings generated will have high impact because the lack of targeted therapies for TNBC presents a great unmet clinical need and could be transformative to improve patient outcomes.


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: 2026 ( Subtotal = $0 )
2026	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	5	2/13/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $488,057 )
2025	2025	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	001	6	8/28/2025	COMPETING CONTINUATION	$488,057
2025	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	5	8/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $488,057

Issue Date FY: 2024 ( Subtotal = $380,449 )
2024	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	5	4/12/2024	NON-COMPETING CONTINUATION	$380,449
														Subtotal = $380,449

Issue Date FY: 2023 ( Subtotal = $419,927 )
2023	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	4	5/3/2023	NON-COMPETING CONTINUATION	$419,927
														Subtotal = $419,927

Issue Date FY: 2022 ( Subtotal = $431,028 )
2022	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	3	4/26/2022	NON-COMPETING CONTINUATION	$431,028
														Subtotal = $431,028

Issue Date FY: 2021 ( Subtotal = $404,685 )
2021	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	2	5/12/2021	NON-COMPETING CONTINUATION	$404,685
														Subtotal = $404,685

Issue Date FY: 2020 ( Subtotal = $417,301 )
2020	2020	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Cancer Biology Research	000	1	7/17/2020	NEW	$417,301
														Subtotal = $417,301

Grand Total All Awards = $2,541,447

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Role of microbial-modulated bile acid receptor signaling in breast cancer

Award Number: R01CA253329

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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