Thursday, January 22, 2026 1/22/2026

Role of Ly6K in TGF-beta and immune escape pathways of triple negative breast cancer

Award Number: R01CA227694
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/03/2018
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Role of Ly6K in TGF-beta and immune escape pathways of triple negative breast cancer - Project Summary/abstract We have identified that increased expression of Ly6K is associated with poor outcome in triple negative breast cancer (TNBC). Mechanistically, Ly6K is required for activation of TGFβ signaling and increased expression of the immune checkpoint protein PD-L1. We propose that the biomarker Ly6K is an ideal therapeutic target for the treatment of TNBC because this protein is not expressed in normal cells, except in testis, and it is not required for vital organ function, except for spermatogenesis. Thus, targeting this protein for the treatment of TNBC, a disease affecting mostly females, is appropriate and ideal. We have identified small drug-like molecules, which specifically bind to Ly6K and inhibit in vivo tumor growth. Mechanistically, they inhibit TGFβ signaling and PD- L1 expression in TNBC cells in an Ly6K dependent manner. In this proposal, we plan to validate these potential novel therapeutics in a humanized PDX model. This proposal will reveal the missing signaling links downstream of Ly6K, which activate TGFβ signaling and increase PD-L1 expression. We anticipate that the findings from our research will transform the field of developmental therapeutics concerning treatment of TNBC by defining Ly6K as a novel therapeutic target for anti-TGFβ signaling and inhibition of PD-L1 expression.


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 = -$24,447 )
2026	2022	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	5	1/5/2026	NON-COMPETING CONTINUATION	-$24,447
														Subtotal = -$24,447

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	5	7/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $388,498 )
2022	2022	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	5	7/31/2022	NON-COMPETING CONTINUATION	$388,498
														Subtotal = $388,498

Issue Date FY: 2021 ( Subtotal = $399,241 )
2021	2021	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	4	7/19/2021	NON-COMPETING CONTINUATION	$399,241
														Subtotal = $399,241

Issue Date FY: 2020 ( Subtotal = $398,541 )
2020	2020	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	3	8/4/2020	NON-COMPETING CONTINUATION	$398,541
														Subtotal = $398,541

Issue Date FY: 2019 ( Subtotal = $389,208 )
2019	2019	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	001	2	8/2/2019	NON-COMPETING CONTINUATION	$389,208
2019	2018	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	1	11/19/2018	NEW	$0
														Subtotal = $389,208

Issue Date FY: 2018 ( Subtotal = $367,045 )
2018	2018	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Cancer Biology Research	000	1	8/3/2018	NEW	$367,045
														Subtotal = $367,045

Grand Total All Awards = $1,918,086

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Role of Ly6K in TGF-beta and immune escape pathways of triple negative breast cancer

Award Number: R01CA227694

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/03/2018

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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