Sunday, February 15, 2026 2/15/2026

Lipid metabolism as a therapeutic vulnerability in BET inhibitor-resistant medulloblastoma

Award Number: F32CA261034
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2024

Group Awards By:

View Award Description

Lipid metabolism as a therapeutic vulnerability in BET inhibitor-resistant medulloblastoma - Project Summary/Abstract MYC-driven medulloblastomas are a particularly devastating group of pediatric brain tumors that exhibit resistance and continued progression despite standard of care treatments. Our preclinical work[1] identified BET-bromodomain inhibitors as a potentially promising new class of drugs for children with medulloblastoma (MB) and other MYC-driven cancers, providing rationale to evaluate these agents in clinical trials. However, treatment with BET inhibitor (BETi) alone is unlikely to be sufficient for a cure, with most tumors evolving to acquire resistance to single-agent targeted therapies. An attractive strategy to overcoming therapy resistance is to identify and exploit new vulnerabilities that exist in drug-tolerant cells. Metabolic pathways are of particular interest in this context as they often rely on few essential enzymes, are frequently “rewired” in cancer cells vs. normal cells, support and drive adaptive resistance to drug, provide essential survival capabilities, and can be easily targeted with pharmacologic inhibitors[3]. Our previous work applied an integrative genomics approach to identify genes and pathways mediating BETi response in MB[2]. These studies revealed that MYC-driven MB cells with acquired resistance to BETi reinstate transcription of essential genes suppressed by drug and exhibit changes in cell-state and new vulnerabilities not present in drug-sensitive cells. We now have a growing body of evidence showing that BET inhibition downregulates the expression of key lipid metabolism genes and metabolism-related signaling pathways, and that MB cells with adaptive resistance to BETi differentially express and exhibit preferential dependency on specific lipid metabolic genes and transcriptional regulators. These findings led me to hypothesize that metabolic reprogramming creates novel vulnerabilities in BETi drug- tolerant MB cells that can be targeted to overcome resistance. The studies described herein will characterize the altered lipid metabolism of BETi-resistant MB cells, assess the impact of BETi-driven metabolic rewiring on cell signaling and the resistance phenotype, and investigate the possibility of exploiting lipid metabolic dependencies as a novel approach to overcome resistance to BETi-targeted therapy.


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 = -$11,850 )
2025	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Research Manpower	000	3	1/23/2025	NON-COMPETING CONTINUATION	-$11,850
														Subtotal = -$11,850

Issue Date FY: 2023 ( Subtotal = $71,792 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Research Manpower	000	3	3/30/2023	NON-COMPETING CONTINUATION	$71,792
														Subtotal = $71,792

Issue Date FY: 2022 ( Subtotal = $67,482 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Research Manpower	001	2	6/22/2022	NON-COMPETING CONTINUATION	$1,092
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Research Manpower	000	2	4/11/2022	NON-COMPETING CONTINUATION	$66,390
														Subtotal = $67,482

Issue Date FY: 2021 ( Subtotal = $65,994 )
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Research Manpower	001	1	3/9/2021	NEW	$0
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Research Manpower	000	1	3/9/2021	NEW	$66,390
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Research Manpower	002	1	8/31/2021	NEW	-$396
														Subtotal = $65,994

Grand Total All Awards = $193,418

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Lipid metabolism as a therapeutic vulnerability in BET inhibitor-resistant medulloblastoma

Award Number: F32CA261034

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer