Thursday, July 3, 2025 7/3/2025

Targeting Fanconi Anemia pathway to overcome platinum drug resistance in ovarian cancer

Award Number: R01CA247684
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

Group Awards By:

View Award Description

Targeting Fanconi Anemia pathway to overcome platinum drug resistance in ovarian cancer - Project Summary Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women and the deadliest gynecological cancer in the United States. The current standard treatment for ovarian cancer consists of surgery followed by platinum drug-based chemotherapy. Platinum drugs could induce DNA interstrand crosslink (ICL), which results in replication fork stalling and thus decrease cell viability. Although most of patients initially respond to platinun drug-based chemotherapy and achieve remission, up to 80% of patients become refractory to platinum drugs over time and ultimately succumb to the disease due to the resistance to platinum-based therapy. Thus, it is urgent to develop novel approaches to overcome platinum drug resistance of ovarian cancer (PROC). Fanconi anemia (FA) pathway is critical to repair ICLs and elevated activity of FA signaling is one of major mechanisms leading to platinum-resistance in ovarian cancer. The role of FA pathway in repair of ICL has been well studied last decade, however, how the regulatory switch from a stalled replication fork caused by platinum drugs to initiation of FA signaling and how FA is activated in PROC cells are poorly understood. To elucidate the mechanism regulating initiation of FA signaling, we have conducted the significant amount of preliminary studies to demonstrate that And-1 is critical for activation of FA signaling and FA- mediated platinum drug resistance in ovarian cancer. The major objective of this proposal is to determine the mechanism of how And-1-FANCM axis regulates FA signaling and platinum resistance in PROC. Here, we propose three specific aims. Aim 1: Determine how And-1 promotes the switch from stalled replication forks to initiation of FA signaling at ICLs. Aim 2: Determine the role of And-1 in the regulation of platinum drug resistance in PROC cells. Aim 3: Evaluate the effects of And-1 inhibition on platinum drug resistance using orthotopic PROC PDX and syngeneic models. The completion of proposed studies will not only elucidate a novel mechanism regulating platinum resistance in PROC, but also provide an innovative therapeutic strategy as well as a new potential drug for treatment of PROC patients.


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 = $392,347 )
2025	2025	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	5	3/14/2025	NON-COMPETING CONTINUATION	$392,347
														Subtotal = $392,347

Issue Date FY: 2024 ( Subtotal = $414,143 )
2024	2024	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	4	3/20/2024	NON-COMPETING CONTINUATION	$392,347
2024	2024	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	001	4	4/17/2024	NON-COMPETING CONTINUATION	$21,796
														Subtotal = $414,143

Issue Date FY: 2023 ( Subtotal = $427,221 )
2023	2023	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	3	2/28/2023	NON-COMPETING CONTINUATION	$427,221
														Subtotal = $427,221

Issue Date FY: 2022 ( Subtotal = $427,218 )
2022	2022	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	2	3/31/2022	NON-COMPETING CONTINUATION	$427,218
														Subtotal = $427,218

Issue Date FY: 2021 ( Subtotal = $435,940 )
2021	2021	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	1	4/14/2021	NEW	$435,940
														Subtotal = $435,940

Grand Total All Awards = $2,096,869

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting Fanconi Anemia pathway to overcome platinum drug resistance in ovarian cancer

Award Number: R01CA247684

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer