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Investigating serum exosomal annexin A2 in promoting aggressive TNBC in African American women

Award Number: R01CA220273
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Investigating serum exosomal annexin A2 in promoting aggressive TNBC in African American women - Project Abstract Triple negative breast cancer (TNBC) affects women of African descent three times more than women of European descent. African American women with TNBC have poor survival and high mortality rates. Metastasis to distant vital organs such as bone, lung, and brain is the most devastating feature of TNBC. It is critical to investigate the molecular mechanism(s) that lead to aggressive disease in patients with TNBC so that improved therapeutic options can be developed. Emerging evidence suggests that tumor-derived exosomes are mediators of tumorigenesis and tissue-specific metastasis by contributing to the establishment of a pre- metastatic niche. Annexin A2 (AnxA2) is an often identified exosomal protein whose elevated levels are seen in TNBC patient sera and cell lines. Exosomal AnxA2 (exo-AnxA2) is more highly expressed in African American (AA) TNBC patients than in Caucasian TNBC patients resulting in reduced survival. Our recent data suggest a role for exo-AnxA2 in establishing a pre-metastatic niche which subsequently promotes breast cancer metastasis. The long-term goal of our research is to develop improved therapeutic options for aggressive TNBC that disproportionately affects AA patients. Our hypothesis for the proposed studies is that exo-AnxA2 is a determinant of the aggressiveness of TNBC metastasis and contributes to poor prognosis in AA patients with TNBC. The premise for this hypothesis stems from the literature (2, 6-9,11) and our published data indicating that exo-AnxA2 creates a pre-metastatic niche that may drive aggressive TNBC metastasis. We will address this hypothesis by the following three specific aims: Aim 1: Evaluate differences in the association of exo-AnxA2 expression with measures of disease aggressiveness among racially distinct populations. Aim 2: Determine whether exo-AnxA2 promotes aggressive TNBC metastasis. Aim 3: Determine the mechanism(s) that drives exo-AnxA2-mediated metastatic niche formation and aggressive tumors in TNBC. The impact of the proposed studies is the likely identification of a novel secreted and exosomal protein as a functional regulator of long-range communications between metastatic tumors and the target stromal microenvironment. Moreover, due to their extracellular location, secreted AnxA2 and partner proteins represent potential prognostic agents and therapeutic targets. Thus, we expect this research to open up exciting new avenues of clinical translation in metastasis detection, prognosis, and therapy for TNBC patients.


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 = -$23,074 )
2026	2022	THE UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	6	12/2/2025	NON-COMPETING CONTINUATION	-$23,074
														Subtotal = -$23,074

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	THE UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	6	7/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $249,552 )
2022	2022	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	6	6/10/2022	NON-COMPETING CONTINUATION	$249,552
														Subtotal = $249,552

Issue Date FY: 2021 ( Subtotal = $367,118 )
2021	2021	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	5	6/9/2021	NON-COMPETING CONTINUATION	$367,118
														Subtotal = $367,118

Issue Date FY: 2020 ( Subtotal = $367,118 )
2020	2020	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	4	6/11/2020	NON-COMPETING CONTINUATION	$367,118
														Subtotal = $367,118

Issue Date FY: 2019 ( Subtotal = $106,980 )
2019	2019	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	3	8/23/2019	NON-COMPETING CONTINUATION	$106,980
														Subtotal = $106,980

Issue Date FY: 2018 ( Subtotal = $368,976 )
2018	2018	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	2	6/12/2018	NON-COMPETING CONTINUATION	$368,976
														Subtotal = $368,976

Issue Date FY: 2017 ( Subtotal = $380,476 )
2017	2017	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Cancer Biology Research	000	1	6/14/2017	NEW	$380,476
														Subtotal = $380,476

Grand Total All Awards = $1,817,146

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Investigating serum exosomal annexin A2 in promoting aggressive TNBC in African American women

Award Number: R01CA220273

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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