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TAZ-driven Regulation of Tumor Microenvironment in Triple-Negative Breast Cancer

Award Number: R03CA286634
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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TAZ-driven Regulation of Tumor Microenvironment in Triple-Negative Breast Cancer - ABSTRACT Breast cancer (BC) is a complex and heterogeneous neoplastic disease with a high incidence and mortality. BC can be divided into clinical, histopathologic, and molecular subtypes. Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancer cases and is characterized by tumors that do not express the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is thought to be the most aggressive subtype and is associated with a poor prognosis, as well as a high risk of distant recurrence and death within the first 3–5 years of follow-up. The absence of these receptors renders TNBC resistant to treatments targeting those pathways. Thus, TNBC still remains a neoplastic disease with unmet clinical challenges. Our laboratory has previously demonstrated an integral tumor-intrinsic role of TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1), which is a key component of the Hippo signaling pathway found in TNBC progression/metastasis. New preliminary data in our laboratory indicate that tumor TAZ expression inhibits tumor progression in mouse models of TNBC cells in immune system intact mice, thus indicating that TAZ expression also plays an underappreciated extrinsic role in TNBC biology. We further revealed that TAZ regulates the recruitment and/or function of immune suppressive cells, such as myeloid-derived suppressor cells (MDSCs), macrophages and regulatory T cells (Tregs). The overall objective of this proposal is to understand the underlying molecular mechanisms by which TAZ expression in tumor cells regulates immune suppressive cells in TNBC. Our central hypothesis is that tumor TAZ expression regulates the TME landscape via cross-talk between cancer cells with non-cancer immune suppressive cells. Our long-term goal is to decipher TAZ regulated crosstalk between breast tumor cells and the immune components within the tumor microenvironment (TME) to uncover new prognostic or therapeutic targets for TNBC. To achieve these goals, we propose the following two aims: 1) To determine the impact of tumor-intrinsic TAZ expression on the immune-TME; and 2) To understand the molecular mechanisms of TAZ expression driven immune suppressive cells recruitment in TME. A major impact of this study is to identify previously undescribed TAZ-mediated mechanisms that will unveil new biomarkers or inform novel therapeutic interventions for advanced TNBC.


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 = $78,125 )
2025	2025	UNIVERSITY OF TOLEDO	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	001	3	12/23/2024	NON-COMPETING CONTINUATION	$78,125
2025	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Cancer Biology Research	000	1	12/20/2024	NEW	$0
														Subtotal = $78,125

Issue Date FY: 2024 ( Subtotal = $86,750 )
2024	2024	HEALTH RESEARCH, INC.	ELM & CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Cancer Biology Research	000	1	12/6/2023	NEW	$86,750
2024	2024	UNIVERSITY OF TOLEDO	3000 ARLINGTON AVE	TOLEDO	OH	43614	LUCAS	USA	Cancer Biology Research	002	2	9/10/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$49,202
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Cancer Biology Research	001	1	9/9/2024	NEW	-$49,202
														Subtotal = $86,750

Grand Total All Awards = $164,875

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TAZ-driven Regulation of Tumor Microenvironment in Triple-Negative Breast Cancer

Award Number: R03CA286634

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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