Project Grant R21CA313738

The National Institutes of Health National Cancer Institute awarded The University of Texas Southwestern Medical Center $426,828 on August 6, 2026, under the Cancer Treatment Research program (CFDA 93.395) to investigate jumonji lysine demethylase enzymes as therapeutic targets in small cell lung cancer.

The research evaluates jumonji demethylases as key contributors to SCLC development and acquired resistance to therapy. The work employs genetically engineered mouse models representing both ASCL1-high and NEUROD1-high SCLC subtypes to test two inhibitors: JIB-04, a pan-jumonji inhibitor with established xenograft efficacy, and TACH101, a jumonji KDM4 inhibitor in clinical trials for other cancers. The research applies these inhibitors as first-line therapy, as second-line treatment following etoposide/cisplatin, and in combination with immune checkpoint inhibitors. The project will define the transcriptional action of these inhibitors in vivo and determine when jumonji KDMs become activated during SCLC onset and progression. The use of immunocompetent animal models addresses the limitation that human specimens cannot adequately represent the full progression of SCLC development and the onset of therapeutic resistance.

Performance occurs in Dallas, Texas. The project period runs from the award date through July 31, 2028. This is a Project Grant, the assistance type under which NIH supports investigator-initiated biomedical research.