Wednesday, August 20, 2025 8/20/2025

Targeting BPTF in the Therapy of BRAF-mutant Melanoma

Award Number: R01CA215755
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/17/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2023

Group Awards By:

View Award Description

Targeting BPTF in the Therapy of BRAF-mutant Melanoma - The successful development of targeted therapy for BRAF-mutant melanoma represented a landmark in cancer therapy. However, despite impressive initial responses, most melanoma patients eventually progressed on therapy, necessitating the development of additional therapeutic strategies. Recent studies from our laboratory have identified novel roles for the bromodomain plant homeodomain (PHD) finger transcription factor [BPTF] gene as a mediator of melanoma progression, and as a potential target for therapy. Our studies showed that BPTF activates the MAP kinase pathway, resulting in decreased sensitivity to BRAF inhibitors. Separately, the development of a small molecule inhibitor targeting the BET family has indicated the druggability of bromodomain motifs. In this proposal, we plan to further develop BPTF targeting as a therapeutic strategy for advanced melanoma, especially in combination with available therapies targeting mutant BRAF. Our three specific aims are: Aim 1: To determine the role of BPTF targeting in melanoma therapy. To develop BPTF targeting as a therapeutic strategy for melanoma, we will assess the anti-tumor efficacy of BPTF targeting using (i) bromosporine, a pan-bromodomain inhibitor with demonstrated affinity for BPTF, and (ii) AU1, a novel, small molecule that selectively targets the BPTF bromodomain. We will assess the anti-tumor efficacy of these compounds in a panel of human melanoma cell lines and patient-derived xenografts (PDX) both in culture and in vivo. Aim 2: To determine the role of combined targeting of BPTF and BRAF in melanoma therapy. To develop combined targeting of BPTF and BRAF as a rational strategy for melanoma therapy, we will examine BPTF targeting with bromosporine or AU1 in combination with BRAF pathway inhibition in a panel of human melanoma cell lines and PDXs both in cell culture and in vivo. In addition, we will assess the ability of both BPTF inhibitors to sensitize melanoma PDXs from patients progressing on BRAF inhibitor therapy both in culture and in vivo. Aim 3: To characterize the functional role of BPTF targeting in melanoma cells. We will determine whether BPTF binds to the ERK promoter. We will determine the effects of BPTF targeting (alone or in combination with BRAF inhibitors) on expression of downstream markers in melanoma cells. Finally, we will determine whether targeting BPTF interferes with its interaction with histone modifications. These studies will establish BPTF targeting as a viable strategy for the therapy of melanoma, especially in combination with BRAF inhibitors.


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 = -$336 )
2024	2021	SUTTER BAY HOSPITALS	475 BRANNAN ST STE 130	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	000	5	1/9/2024	NON-COMPETING CONTINUATION	-$336
														Subtotal = -$336

Issue Date FY: 2021 ( Subtotal = $617,648 )
2021	2021	SUTTER BAY HOSPITALS	633 FOLSOM ST FL 5	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	000	5	2/1/2021	NON-COMPETING CONTINUATION	$617,648
														Subtotal = $617,648

Issue Date FY: 2020 ( Subtotal = $617,648 )
2020	2020	SUTTER BAY HOSPITALS	633 FOLSOM ST FL 5	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	000	4	2/25/2020	NON-COMPETING CONTINUATION	$617,648
														Subtotal = $617,648

Issue Date FY: 2019 ( Subtotal = $599,119 )
2019	2019	SUTTER BAY HOSPITALS	633 FOLSOM ST FL 5	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	000	3	2/12/2019	NON-COMPETING CONTINUATION	$599,119
														Subtotal = $599,119

Issue Date FY: 2018 ( Subtotal = $617,524 )
2018	2018	SUTTER BAY HOSPITALS	633 FOLSOM ST FL 5	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	001	2	5/23/2018	NON-COMPETING CONTINUATION	$61,752
2018	2018	SUTTER BAY HOSPITALS	633 FOLSOM ST FL 5	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	000	2	2/16/2018	NON-COMPETING CONTINUATION	$555,772
														Subtotal = $617,524

Issue Date FY: 2017 ( Subtotal = $614,787 )
2017	2017	SUTTER BAY HOSPITALS	633 FOLSOM STREET 5TH FLOOR	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Cancer Treatment Research	000	1	3/17/2017	NEW	$614,787
														Subtotal = $614,787

Grand Total All Awards = $3,066,390

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting BPTF in the Therapy of BRAF-mutant Melanoma

Award Number: R01CA215755

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/17/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer