Wednesday, January 15, 2025 1/15/2025

Stromal Regulation of Basal Cell Carcinoma Formation

Award Number: R01AR046786
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary Non-melanoma skin cancer, the most common US tumor, encompasses basal cell (BCC) and squamous cell (SCC) carcinomas, and leads to extensive morbidity and mortality. ARO46786 now in its 20th year, has focused on BCC-to-SCC transition (BST) a common but understudied resistance mechanism that represents a significant challenge to therapy and poorer outcomes. We propose five major BST Keratocarcinoma (KC) cell states and show that combinatorial AP-1 and SRF co-factor interactions provide the transcriptional switch from HH sensitivity to RAS-MAPK dependence and that c-FOS-driven BST appears reversible. By contrast, interrogation of stromal heterogeneity identified a skin cancer-associated macrophage (SCAM) required for BCC growth in allografts and organoids. SCAMs are self-propagating, transplantable, and long-lived in the BCC tumor environment. Tumor- associated macrophages have been shown to have proliferative and anti-immune checkpoint activity highlighting the gap in knowledge about the skin microenvironment. These preliminary studies support our overarching hypothesis that BST and SCAMs mediate BCC tumor evolution and resistance. To further test this hypothesis, ARO46786 will: Elucidate the drivers and sensitivities of BST by refining the KC chromatin and tumor dependency map and elucidating the mechanism of the reversible BST transcription factor switch; and elucidate the origin and function of SCAMs in BCC growth by dissecting SCAM function on tumor epithelial growth and identifying the determinants of SCAM polarization and function. Project completion will fill major gaps in our understanding how the tumor epithelium and microenvironment contribute to resistance, and lead to the nomination of novel cancer therapies.


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: 2024 ( Subtotal = $527,389 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	23	6/13/2024	NON-COMPETING CONTINUATION	$38,058
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	23	3/8/2024	NON-COMPETING CONTINUATION	$489,331
														Subtotal = $527,389

Issue Date FY: 2023 ( Subtotal = $549,316 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	22	3/31/2023	NON-COMPETING CONTINUATION	$549,316
														Subtotal = $549,316

Issue Date FY: 2022 ( Subtotal = $554,038 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	21	9/7/2022	COMPETING CONTINUATION	$101,272
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	21	7/1/2022	COMPETING CONTINUATION	$554,038
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	20	9/7/2022	NON-COMPETING CONTINUATION	-$101,272
														Subtotal = $554,038

Issue Date FY: 2021 ( Subtotal = $346,820 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	20	3/29/2021	NON-COMPETING CONTINUATION	$321,791
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	20	5/18/2021	NON-COMPETING CONTINUATION	$25,029
														Subtotal = $346,820

Issue Date FY: 2020 ( Subtotal = $329,562 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	19	3/31/2020	NON-COMPETING CONTINUATION	$329,562
														Subtotal = $329,562

Issue Date FY: 2019 ( Subtotal = $356,797 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	18	4/3/2019	NON-COMPETING CONTINUATION	$356,797
														Subtotal = $356,797

Issue Date FY: 2018 ( Subtotal = $356,443 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	17	4/14/2018	NON-COMPETING CONTINUATION	$356,443
														Subtotal = $356,443

Issue Date FY: 2017 ( Subtotal = $356,099 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	16	2/17/2017	COMPETING CONTINUATION	$356,099
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	16	6/13/2017	COMPETING CONTINUATION	$117,649
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	15	6/13/2017	EXTENSION WITH OR WITHOUT FUNDS	-$117,649
														Subtotal = $356,099

Issue Date FY: 2016 ( Subtotal = $363,595 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	3/15/2016	EXTENSION WITH OR WITHOUT FUNDS	$363,595
														Subtotal = $363,595

Issue Date FY: 2015 ( Subtotal = $363,197 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	3/17/2015	NON-COMPETING CONTINUATION	$363,197
														Subtotal = $363,197

Issue Date FY: 2014 ( Subtotal = $355,558 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	13	8/14/2014	NON-COMPETING CONTINUATION	$355,558
														Subtotal = $355,558

Issue Date FY: 2013 ( Subtotal = $345,054 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	12	7/14/2013	NON-COMPETING CONTINUATION	$18,123
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	12	4/12/2013	NON-COMPETING CONTINUATION	$326,201
2013	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	11	4/12/2013	COMPETING CONTINUATION	$730
														Subtotal = $345,054

Issue Date FY: 2012 ( Subtotal = $359,090 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	11	4/16/2012	COMPETING CONTINUATION	$361,096
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	11	5/11/2012	COMPETING CONTINUATION	-$2,006
2012	2010	STANFORD UNIVERSITY	616 SERRA STREET	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	4/16/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $359,090

Issue Date FY: 2010 ( Subtotal = $326,450 )
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	7/30/2010	NON-COMPETING CONTINUATION	$326,450
														Subtotal = $326,450

Issue Date FY: 2009 ( Subtotal = $328,698 )
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	7/27/2009	NON-COMPETING CONTINUATION	$328,698
														Subtotal = $328,698

Issue Date FY: 2008 ( Subtotal = $327,682 )
2008	2008	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	7/24/2008	NON-COMPETING CONTINUATION	$327,682
														Subtotal = $327,682

Issue Date FY: 2007 ( Subtotal = $333,362 )
2007	2007	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	8/10/2007	NON-COMPETING CONTINUATION	$333,362
														Subtotal = $333,362

Issue Date FY: 2006 ( Subtotal = $338,278 )
2006	2006	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	9/15/2006	COMPETING CONTINUATION	$338,278
														Subtotal = $338,278

Issue Date FY: 2005 ( Subtotal = $335,954 )
2005	2005	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/17/2005	NON-COMPETING CONTINUATION	$335,954
														Subtotal = $335,954

Issue Date FY: 2004 ( Subtotal = $335,940 )
2004	2004	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	5/18/2004	NON-COMPETING CONTINUATION	$335,940
														Subtotal = $335,940

Grand Total All Awards = $8,491,648

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Stromal Regulation of Basal Cell Carcinoma Formation

Award Number: R01AR046786

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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