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SR-A as a therapeutic target in breast cancer

Award Number: R21CA280448
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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SR-A as a therapeutic target in breast cancer - ABSTRACT Tumor-associated macrophages are critical regulators of tumor development, progression, and metastasis. Factors in the tumor microenvironment induce tumor-associated macrophages to adopt a tumor-supportive phenotype that suppresses immune responses. The accumulation of tumor-supportive macrophages in tumors is associated with accelerated tumor progression and a poor patient prognosis. Macrophages sense and respond to their environment by expressing pattern-recognition receptors such as Class-A Scavenger Receptors (SR-A). In preliminary data, we show that SR-A binds to glycans expressed on breast cancer cells but not on non-cancer cells. Furthermore, we show that SR-A expression promotes the development of palpable tumors and lung metastases in mouse models that spontaneously develop breast cancer. Importantly, results from gene expression profiling indicate that tumor-associated macrophages adopt an immune-suppressive phenotype in SR-A-expressing mice but not in SR-A knock-out mice. These findings support the novel conclusion that SR-A binding to tumor-specific ligands induces the polarization of tumor-infiltrating macrophages toward an immune- suppressive phenotype that enhances breast cancer growth and metastases. It logically follows that inhibiting SR-A interactions in tumors may provide an innovative approach that repolarizes TAMs to an antitumor phenotype, improves the effectiveness of anti-tumor immune response, and inhibits breast cancer progression. Thus, the goals of the proposed experiments are to i) identify the ligands on breast cancer cells that bind SR-A and induce macrophage polarization toward a protumor phenotype, and ii) demonstrate that antagonizing SR-A repolarizes macrophages toward a tumor-inhibitory phenotype, enhances the immune response, and prolongs survival in preclinical models of breast cancer. Showing that antagonizing SR-A interactions increases anti-tumor immune activity and prolongs survival in animal models will confirm the therapeutic potential of this approach to treat breast cancer. In addition, identifying tumor-associated ligands that interact with SR-A may suggest additional tumor-specific strategies for inhibiting these interactions.


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 = $178,819 )
2025	2025	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Treatment Research	001	2	6/12/2025	NON-COMPETING CONTINUATION	$17,881
2025	2025	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Treatment Research	000	2	12/3/2024	NON-COMPETING CONTINUATION	$160,938
														Subtotal = $178,819

Issue Date FY: 2024 ( Subtotal = $214,583 )
2024	2024	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Treatment Research	000	1	12/20/2023	NEW	$214,583
														Subtotal = $214,583

Grand Total All Awards = $393,402

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SR-A as a therapeutic target in breast cancer

Award Number: R21CA280448

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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