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

Jumonji KDM4A drives targetable oncogenic programs in small cell lung cancer

Award Number: R21CA280319
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

Jumonji KDM4A drives targetable oncogenic programs in small cell lung cancer - Abstract Small cell lung cancer (SCLC) is a recalcitrant disease that rapidly acquires drug resistance and for which no mechanistically novel drug therapies have been developed over the last several decades. SCLC responds poorly to second line therapy or immunotherapy. There is therefore a challenging yet impactful opportunity to discover new therapeutic strategies against this recalcitrant tumor type. A major obstacle to accomplishing this goal is that over 500 drugs under clinical development have shown no benefit over current first line etoposide treatment. We have highly promising preliminary data in cell culture and in vivo models that strongly support that epigenetic enzymes of the Jumonji lysine demethylase family (Jumonji KDMs) constitute viable druggable targets in SCLC, and even in disease that has acquired chemotherapy resistance. Here we therefore propose a new idea: that Jumonji demethylases are key contributors to SCLC and to its fast-acquired resistance to therapy. We have novel tools to probe this idea pharmacologically: namely, enzyme inhibitors developed by us with proven in vivo efficacy. Thus, we propose an innovative three-pronged therapeutic paradigm: treating SCLC with Jumonji inhibitors as first line therapy, treating SCLC resistant to etoposide with second line Jumonji inhibitors alone or in combination with other agents for which we have a biological rationale (including mTOR inhibitors because of the gene expression profiles we observe in treated cells), and combining Jumonji inhibitors with standard first line therapy upfront to prevent therapeutic resistance in the first place. Mechanistically, the impact of pharmacological or genetic inhibition of Jumonji KDM4A on the SCLC epigenome and transcriptome will be defined. Our preliminary data demonstrates that SCLC cell lines and xenografts, including etoposide resistant SCLC cells, are sensitive to the pan-Jumonji inhibitor JIB-04 and to the Jumonji KDM4 subfamily inhibitor SD-70, through on-target activity. Furthermore, we show that Jumonji inhibition alters levels of the neuroendocrine transcription factors that drive SCLC oncogenesis. Thus we hypothesize that Jumonji inhibition will block SCLC growth and overcome therapeutic resistance in clinically relevant disease models, by reprogramming neuroendocrine lineage transcription factor gene programs. This work will thus open a new paradigm for SCLC treatment.


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 = $230,010 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Treatment Research	000	2	3/20/2026	NON-COMPETING CONTINUATION	$230,010
														Subtotal = $230,010

Issue Date FY: 2025 ( Subtotal = $191,675 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Treatment Research	000	1	3/31/2025	NEW	$191,675
														Subtotal = $191,675

Grand Total All Awards = $421,685

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Jumonji KDM4A drives targetable oncogenic programs in small cell lung cancer

Award Number: R21CA280319

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer