Project Grant R01CA292020
- This $214,583 Project Grant awarded by the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) to Tulane University will fund research to evaluate the role of the extracellular matrix in triple-negative breast cancer (TNBC) progression and treatment response, with a focus on African American patient populations. The research aims to provide insights on key extracellular matrix proteins that regulate TNBC tumorigenesis, metastasis, and response to therapy, using 3D in...
- This $3.3 million project grant from the National Cancer Institute's Cancer Cause and Prevention Research program (CFDA 93.393) supports research to identify prediagnostic exposures, germline genetics, and immune and mutational profiles associated with triple negative breast cancer (TNBC). Joan & Sanford I Weill Medical College of Cornell University is the primary awardee and will perform whole exome sequencing of tumor and germline DNA from 400 TNBC patients across four prospective cohort...
- This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $631,492 to support research at the University of Kentucky Research Foundation aimed at identifying nicotinamide N-methyltransferase (NNMT) as a new target to treat triple-negative breast cancer (TNBC). The 5-year project, awarded on April 7, 2025 and scheduled for completion by March 31, 2030, will: Define how NNMT promotes anchorage-independent growth and protects TNBC cells...
- This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $619,764 to the University of Wisconsin - Madison to develop new combination immunotherapy strategies for treating triple-negative breast cancer (TNBC). The key objectives are to: 1) increase the tumor-selective accumulation of a platelet-mediated immune checkpoint inhibitor (P-aPDL1) by triggering local thrombus formation in TNBC tumors, and 2) modulate the immunosuppressive...
- The U.S. National Cancer Institute (NCI) awarded a $400,000 Project Grant under the Cancer Treatment Research federal grant program (CFDA 93.395) to Promilead, LLC for the project "ACTIVATING TFEB TO ENHANCE THE EFFICACY OF IMMUNOTHERAPY FOR TRIPLE NEGATIVE BREAST CANCER". The project aims to investigate the tumor suppressive role of the transcription factor TFEB and its potential to enhance the efficacy of immune checkpoint inhibitor (ICI) immunotherapy for the treatment of triple...
- This Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides $164,500 to The Trustees of Columbia University in the City of New York to investigate the mechanisms by which the protein S100A9 mediates brain metastasis in epidermal growth factor receptor (EGFR)-mutant lung cancer. The key goals are to: Examine how S100A9 expression is epigenetically regulated by histone methylation and the MEIS1 transcription factor in brain metastasis-prone cells....
- The National Cancer Institute (NCI) awarded a 5-year, $676,584 Project Grant under the Cancer Biology Research program (CFDA 93.396) to The University of Texas MD Anderson Cancer Center (MD Anderson). The grant aims to investigate the genomic evolution and tumor microenvironment dynamics that drive metastatic progression in triple-negative breast cancer (TNBC). Specifically, the project will leverage a postmortem tissue collection program and advanced single-cell genomics techniques to...
- This $412,054 federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) will support research at New York University (NYU) to dissect the role of the immune microenvironment in melanoma bone metastasis. The funded research aims to utilize preclinical murine models to define the mechanisms by which melanoma cells colonize the skeletal system and modify the bone microenvironment. Key objectives include examining the role of bone...
- The National Cancer Institute awarded a Project Grant of $151,040.00 to the Dana-Farber Cancer Institute, Inc. (DFCI) under the Cancer Research Manpower (CFDA 93.398) federal grant program. The project, titled "Interrogating the Role of IFNgamma in Promoting Metastasis and Immune Evasion of Triple Negative Breast Cancer," aims to study how interferon gamma (IFNγ) signaling regulates the ability of triple negative breast cancer (TNBC) cells to evade the immune system and establish...
- This Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides funding to the University of Colorado-Denver to study the role of the EYA3/PP2A protein complex in regulating the metastatic spread of triple-negative breast cancer (TNBC). The $647,118 award, effective March 1, 2025 through February 28, 2030, supports research aimed at understanding how EYA3 and its interaction with the B55A subunit of PP2A contribute to TNBC metastasis. The project...
UNRAVEL THE NOVEL ROLE OF S100A7 AND ITS FUNCTIONAL PARTNERS IN METASTATIC TRIPLE NEGATIVE BREAST CANCER RACIAL DISPARITY - TRIPLE-NEGATIVE BREAST CANCER (TNBC) DISPROPORTIONATELY AFFECTS AFRICAN AMERICAN (AA) WOMEN, WITH MORTALITY RATES 65% HIGHER THAN CAUCASIAN (CA) WOMEN. THE MECHANISMS UNDERLYING THE HEIGHTENED AGGRESSIVENESS AND METASTASIS IN AA TNBC REMAIN ELUSIVE. THIS STUDY INVESTIGATES THE IMMUNE SUPPRESSIVE TUMOR MICROENVIRONMENT (TME) AS A DRIVING FACTOR IN AA TNBC PROGRESSION. SPECIFICALLY, IT DELVES INTO THE NOVEL ROLE OF THE S100A7 AND ITS INTERPLAY WITH INTRINSIC IFNG SIGNALING, ELUCIDATING THEIR IMPACT ON TNBC AGGRESSIVENESS AND METASTASIS IN AA WOMEN. OUR RECENT FINDINGS REVEAL ELEVATED S100A7 EXPRESSION IN AA TNBC PATIENT SAMPLES AND CELL LINES RELATIVE TO CA COUNTERPARTS. MOREOVER, HIGHER S100A7 EXPRESSION CORRELATES WITH INCREASED TUMOR BURDEN IN VARIOUS PRE-CLINICAL MODELS, INCLUDING AA TNBC PATIENT-DERIVED XENOGRAFTS (PDX). WE ALSO NOTED THAT S100A7 KNOCKOUT (KO) MOUSE MODELS (GENERATED IN OUR LAB) EXHIBIT REDUCED TUMOR BURDEN, WHILE TREATMENT WITH A NOVEL S100A7-NEUTRALIZING ANTIBODY (NAB) SHOWS PROMISING EFFICACY IN INHIBITING TNBC GROWTH AND METASTASIS. MECHANISTICALLY, S100A7 IS DEMONSTRATED TO ENHANCE CPLA2/PGE2/IFNGR1 SIGNALING IN AA TNBC CELLS, MODULATING INTRINSIC IFNG SIGNALING. THIS PROCESS GENERATES AN IMMUNE SUPPRESSIVE TME BY UPREGULATING PD-L1 AND DOWNREGULATING FAS ON TUMOR CELLS. ADDITIONALLY, AA TNBC TUMOR TISSUES MANIFEST HEIGHTENED IMMUNOSUPPRESSION, CHARACTERIZED BY INCREASED PD-L1 EXPRESSION AND INFILTRATION OF FOXP3+ TREG CELLS. OUR PROPOSED RESEARCH AIMS TO METICULOUSLY UNCOVER HOW S100A7 ORCHESTRATES IFNG RESPONSIVE GENES (PD-L1 AND FAS) TO GENERATE AN IMMUNOSUPPRESSIVE TME IN AA TNBC. THIS INVESTIGATION LEVERAGES DIVERSE AA TNBC CELL LINES, HUMANIZED PDX MODELS, AND GENETICALLY ENGINEERED MOUSE MODELS (GEMMS) OVEREXPRESSING MS100A7, MS100A7 KO, AND THE S100A7 NAB. THE STUDY'S OVERARCHING HYPOTHESIS POSITS THAT S100A7 CONTRIBUTES TO AA TNBC AGGRESSIVENESS BY FOSTERING AN IMMUNOSUPPRESSIVE AND IMMUNE EVASIVE TME VIA REGULATING INTRINSIC IFNG SIGNALING, RESULTING IN PD-L1 UPREGULATION AND FAS DOWNREGULATION. THE RESEARCH STRATEGY ENCOMPASSES THREE KEY AIMS: AIM 1 WILL ELUCIDATE HOW S100A7 SIGNALING REGULATES IFNG RESPONSIVE GENES IN AA TNBC USING AA TNBC CELLS AND MS100A7 GEMMS. AIM 2 WILL DETERMINE THE NOVEL ROLE OF S100A7 IN REGULATING MACROPHAGE PLASTICITY, T CELL FUNCTION, AND FAS-MEDIATED IMMUNE EVASION IN AA TNBC. AIM 3 WILL EVALUATE THE THERAPEUTIC EFFICACY OF S100A7 NAB IN COMBINATION WITH CHEMO OR IMMUNOTHERAPY USING AA TNBC PDOS AND PDX MOUSE MODELS. THIS AIM WILL ALSO DETERMINE THE PROGNOSTIC SIGNIFICANCE OF S100A7 AND ITS DOWNSTREAM SIGNALING MOLECULES IN AA TNBC. IN ADDITION, THIS AIM WILL ESTABLISH THE ASSOCIATION OF S100A7 AND VARIOUS IMMUNE CELLS IN TNBC RACIAL DISPARITY. THE INSIGHTS GAINED ARE POISED TO IDENTIFY NOVEL S100A7-MEDIATED DOWNSTREAM SIGNALING PATHWAYS AND DETERMINE THE CLINICAL RELEVANCE OF S100A7 IN AA TNBC. THIS STUDY HOLDS THE IMMENSE POTENTIAL TO INFORM THE DESIGN OF INNOVATIVE THERAPEUTIC STRATEGIES TAILORED FOR AA TNBC, THEREBY CONTRIBUTING TO IMPROVED OUTCOMES IN THIS HIGH-RISK POPULATION.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $469.5k | 7/22/25 | ||
| Not listed | $469.5k | 6/6/24 |