Monday, June 30, 2025 6/30/2025

RNA Polymerase II as a Therapeutic Target in Acute Myeloid Leukemia (AML) with RAS Signaling Activation

Award Number: R01CA266422
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

Group Awards By:

View Award Description

RNA Polymerase II as a Therapeutic Target in Acute Myeloid Leukemia (AML) with RAS Signaling Activation - PROJECT SUMMARY/ABSTRACT Background: Fms-Like Tyrosine Kinase 3 (FLT3) is the most commonly mutated gene in acute myeloid leukemia (AML) and mutations in FLT3 are associated with high relapse rates. FLT3 tyrosine kinase inhibitors (TKIs) are clinically active in FLT3-mutant AML but duration of response is limited by the development of resistance. Mutations in NRAS and other activation of the RAS pathway are major mechanisms of resistance to FLT3 inhibitors and other AML targeted therapies. Rationale: We have identified suppression of the Mediator/RNA Pol II pathway augments FLT3 TKI-induced apoptosis in the setting of RAS activation. The overall goals of this project are: (1) to prioritize therapeutic targets in the Mediator/RNA Pol II pathway; and (2) to determine the essential Mediator/RNA Pol II-dependent transcriptional targets relevant to FLT3 TKI resistance. Methods: We will identify essential components of the RNA Pol II pathway needed for TKI resistance in AML and evaluate the efficacy of existing RNA Pol II pathway inhibitors in MAPK-activated AML cells. We will determine RNA Pol II-dependent transcriptional changes induced by MAPK activation and FLT3 inhibition in pre-clinical models and patient samples. We will functionally validate the essential downstream transcriptional targets critical to RAS-mediated FLT3 TKI resistance in AML. Expected Results: These studies will rigorously evaluate RNA Pol II as a novel treatment strategy in AML with aberrant RAS/MAPK signaling. If successful, this strategy can be quickly translated to clinical trials in AML and this general approach may also prove efficacious in other RAS-mutant cancers.


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 = $547,180 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	000	4	6/12/2025	NON-COMPETING CONTINUATION	$547,180
														Subtotal = $547,180

Issue Date FY: 2024 ( Subtotal = $600,623 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	001	3	8/1/2024	SUPPLEMENT FOR EXPANSION	$77,113
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Treatment Research	000	3	6/20/2024	NON-COMPETING CONTINUATION	$523,510
														Subtotal = $600,623

Issue Date FY: 2023 ( Subtotal = $534,924 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	2	6/30/2023	NON-COMPETING CONTINUATION	$534,924
														Subtotal = $534,924

Issue Date FY: 2022 ( Subtotal = $550,626 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Treatment Research	000	1	7/1/2022	NEW	$550,626
														Subtotal = $550,626

Grand Total All Awards = $2,233,353

Top

All Categories

About

Search

Reports

Data Submission

Award Information

RNA Polymerase II as a Therapeutic Target in Acute Myeloid Leukemia (AML) with RAS Signaling Activation

Award Number: R01CA266422

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer