Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Exploiting ADAR1-regulated serine metabolism for cancer therapy

Award Number: R21CA313180
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

Group Awards By:

View Award Description

Exploiting ADAR1-regulated serine metabolism for cancer therapy - Project Summary/Abstract Triple-negative breast cancer (TNBC) is characterized by the lack of expression for estrogen, progesterone, and HER2 receptors in the cancer tissues. TNBC is more aggressive, has higher recurrence rate, and is associated with worse prognosis. The mission to develop novel therapies and identify actionable targets remain top priorities in TNBC research. We recently demonstrated an elevated dependency on an RNA editing enzyme, ADAR1, in TNBC cell lines, highlighting ADAR1’s potential as a novel therapeutic target. Through performing a functional antagonism drug screen using an FDA-approved drug library, we discovered that ADAR1 knockdown sensitized TNBC cells to PHGDH inhibition. Biochemical analyses revealed that ADAR1 knockdown reduced serine transport and biosynthesis. To further understand the implication of ADAR1-regulated serine metabolism, we will take a two-prong approach to 1) elucidate the mechanisms underlying ADAR1-regulated serine metabolism, and to 2) explore cancer therapeutic opportunities with ADAR1-regulated serine metabolism. By using an orthotopic implantation mouse model, we will determine if ADAR1-protected serine addiction can be targeted in vivo to suppress tumor progression. By testing the effect of ADAR1 knockdown 1) in combination with other drugs targeting one-carbon metabolism or 2) in other PHGDHi-resistant cancer cells, we aim to demonstrate the potential of exploiting ADAR1-associated metabolic vulnerabilities for cancer treatment. If successful, this project will achieve both the short-term goal of identifying mechanistic connections between ADAR1 activity and serine metabolism, and the long-term goal of unveiling novel therapeutic opportunities against TNBC and other cancer types through ADAR1-regulated metabolic vulnerabilities. We are confident that discoveries generated by our investigation will serve as the foundation for impactful basic, pre-clinical, and ultimately clinical studies to benefit TNBC patients. To corroborate in vitro cell activity results, preclinical in vivo mouse models are necessary, especially for novel synergy-based strategies described in this proposal. By using both pharmacological and dietary interventions in a mouse orthotopic tumor implantation model, we present a comprehensive strategy to demonstrate the effect of ADAR1-protected serine addiction.


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 = $399,829 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Treatment Research	000	1	6/30/2026	NEW	$399,829
														Subtotal = $399,829

Grand Total All Awards = $399,829

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Exploiting ADAR1-regulated serine metabolism for cancer therapy

Award Number: R21CA313180

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer