Tuesday, July 1, 2025 7/1/2025

Targeting the MUC1-C Oncoprotein in Triple-Negative Breast Cancer

Award Number: R01CA097098
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2002
PERIOD OF PERFORMANCE END DATE: 03/31/2029

Group Awards By:

View Award Description

Targeting the MUC1-C Oncoprotein in Triple-Negative Breast Cancer - Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options. Combining chemotherapy with immune checkpoint inhibitors (ICIs) has improved TNBC treatment, supporting the premise that DNA damage resistance and immune evasion are of importance for TNBC progression. Nonetheless, TNBCs often exhibit intrinsic or acquired resistance to these agents, emphasizing the need for developing new strategies for the treatment of recalcitrant advanced TNBCs. Our work supported by this grant has demonstrated that the transmembrane MUC1-C oncoprotein, which is aberrantly expressed in TNBCs, contributes to the cancer stem cell (CSC) state, DNA damage resistance and immune evasion. MUC1-C consists of a 58 aa extracellular domain and a 72 aa cytoplasmic domain that contribute to TNBC progression. These findings have supported the development of agents that target the MUC1-C extracellular and cytoplasmic domains for the treatment of advanced refractory TNBCs. Funding by this grant supported generation of the MAb 3D1 antibody that targets the MUC1-C extracellular domain at a conserved alpha-3 helix. Our work on MAb 3D1 has resulted in the development of allogeneic anti- MUC1-C CAR T cells with pharma that are now in the clinic for the treatment of TNBCs and other cancers. MAb 3D1 is also being developed as an antibody-drug conjugate (ADC) with the NCI NExT Program for IND- enabling studies and early phase evaluation as an immunotherapy for TNBC patients. We anticipate that, as for other anti-cancer agents, patients with TNBC will develop resistance to these anti-MUC1-C MAb 3D1 CAR T cells and ADCs. To address this potential outcome, our proposed work focuses on the development of novel strategies directed against the MUC1-C extracellular domain at a unique conserved alpha-4 helix. Our objective is to develop new immunotherapeutic agents that circumvent potential resistance mechanisms which emerge against the anti-MUC1-C agents already in the clinic. Our work has also focused on the development of agents that target the MUC1-C cytoplasmic domain, which is activated by chronic inflammation and promotes carcinogenesis. We developed the first-in-class GO- 203 inhibitor that blocks this region and thereby the MUC1-C oncogenic function. The proposed studies will focus on the development of GO-203 and other new agents that target the MUC1-C cytoplasmic domain and are delivered to TNBC CSCs using our recently formulated Quatramer platform. Our rationale is that these anti-MUC1-C agents will, like most therapeutics, be limited by resistance mechanisms and that new approaches will be needed for targeting the MUC1-C extracellular and cytoplasmic domains. The hypothesis is that our new anti-MUC1-C agents will be effective when used alone and in combinations with genotoxic and immune-based therapies, which will be addressed in studies of (i) human TNBC CSCs, (ii) GEMMs, and (iii) TNBC tumor specimens with the objective of advancing TNBC treatment.


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 = $462,269 )
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	002	21	5/22/2025	NON-COMPETING CONTINUATION	$46,227
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	001	21	3/7/2025	NON-COMPETING CONTINUATION	$416,042
2025	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	19	2/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $462,269

Issue Date FY: 2024 ( Subtotal = $466,587 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	001	20	3/19/2024	COMPETING CONTINUATION	$466,587
2024	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	19	3/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $466,587

Issue Date FY: 2022 ( Subtotal = $388,836 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	19	7/22/2022	NON-COMPETING CONTINUATION	$388,836
														Subtotal = $388,836

Issue Date FY: 2021 ( Subtotal = $396,771 )
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	18	5/6/2021	NON-COMPETING CONTINUATION	$396,771
														Subtotal = $396,771

Issue Date FY: 2020 ( Subtotal = $396,771 )
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	17	5/1/2020	NON-COMPETING CONTINUATION	$396,771
														Subtotal = $396,771

Issue Date FY: 2019 ( Subtotal = $384,867 )
2019	2019	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	002	16	5/22/2019	NON-COMPETING CONTINUATION	$384,867
2019	2018	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	001	15	10/23/2018	COMPETING CONTINUATION	$13,779
2019	2016	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	14	10/23/2018	EXTENSION WITH OR WITHOUT FUNDS	-$13,779
														Subtotal = $384,867

Issue Date FY: 2018 ( Subtotal = $396,771 )
2018	2018	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	002	15	6/12/2018	COMPETING CONTINUATION	$396,771
2018	2016	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	001	14	6/8/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
2018	2016	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	14	3/20/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $396,771

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	001	14	10/24/2016	EXTENSION WITH OR WITHOUT FUNDS	$2,105
2017	2015	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	13	10/24/2016	NON-COMPETING CONTINUATION	-$2,105
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $363,125 )
2016	2016	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	14	4/15/2016	EXTENSION WITH OR WITHOUT FUNDS	$363,125
														Subtotal = $363,125

Issue Date FY: 2015 ( Subtotal = $363,125 )
2015	2015	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	13	4/20/2015	NON-COMPETING CONTINUATION	$363,125
														Subtotal = $363,125

Issue Date FY: 2014 ( Subtotal = $352,231 )
2014	2014	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	12	4/16/2014	NON-COMPETING CONTINUATION	$352,231
														Subtotal = $352,231

Issue Date FY: 2013 ( Subtotal = $341,338 )
2013	2013	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	002	11	7/3/2013	NON-COMPETING CONTINUATION	$256,003
2013	2013	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	001	11	5/3/2013	NON-COMPETING CONTINUATION	$85,335
2013	2011	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	9	10/17/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $341,338

Issue Date FY: 2012 ( Subtotal = $363,125 )
2012	2012	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Treatment Research	000	10	7/11/2012	COMPETING CONTINUATION	$363,125
														Subtotal = $363,125

Issue Date FY: 2011 ( Subtotal = $358,868 )
2011	2011	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	001	9	5/16/2011	NON-COMPETING CONTINUATION	$25,897
2011	2011	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	9	4/21/2011	NON-COMPETING CONTINUATION	$332,971
														Subtotal = $358,868

Issue Date FY: 2010 ( Subtotal = $369,968 )
2010	2010	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	8	4/23/2010	NON-COMPETING CONTINUATION	$369,968
														Subtotal = $369,968

Issue Date FY: 2009 ( Subtotal = $713,673 )
2009	2009	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	7	5/29/2009	NON-COMPETING CONTINUATION	$369,968
2009	2009	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Recovery Act Research Support	001	7	9/2/2009	SUPPLEMENT FOR EXPANSION	$343,705
														Subtotal = $713,673

Issue Date FY: 2008 ( Subtotal = $369,968 )
2008	2008	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	6	8/5/2008	COMPETING CONTINUATION	$369,968
														Subtotal = $369,968

Issue Date FY: 2006 ( Subtotal = $371,534 )
2006	2006	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	5	5/22/2006	NON-COMPETING CONTINUATION	$371,534
														Subtotal = $371,534

Issue Date FY: 2005 ( Subtotal = $380,475 )
2005	2005	DANA-FARBER CANCER INSTITUTE	44 BINNEY STREET	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	4	8/31/2005	NON-COMPETING CONTINUATION	$380,475
														Subtotal = $380,475

Grand Total All Awards = $8,382,005

Page 1 of 2 (56 items)12

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting the MUC1-C Oncoprotein in Triple-Negative Breast Cancer

Award Number: R01CA097098

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2002

PERIOD OF PERFORMANCE END DATE: 03/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer