Project Grant R01CA296335

Award Date 1/1/25
Completion Date 12/31/29
Dollars Obligated $584K
Federal Grant Program
93.395
Assistance Type
Project Grant
Place of Performance
New York, NY 10065, USA
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This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides funding to the Sloan-Kettering Institute for Cancer Research to investigate the role of EP300 mutations in bladder cancer pathogenesis and drug response. The $583,973 award, effective January 1, 2025 through December 31, 2029, will support three specific aims:

  1. Studying the impact of EP300 loss-of-function mutations on kinase inhibitor resistance using patient-derived urothelial cancer models. This includes identifying mechanisms of STAT3 activation independent of P300 and its effects on FGFR3 dependence.

  2. Identifying genomic alterations, with a focus on EP300 co-mutations, associated with intrinsic resistance to FGFR3 inhibition in pre-treatment bladder cancer samples.

  3. Determining mechanisms of acquired resistance to the FGFR inhibitor erdafitinib using paired pre- and post-treatment tumor and cell-free DNA samples, and testing combination strategies to overcome or delay this resistance.

The overall goal is to define how EP300 mutations impact urothelial cancer pathogenesis and systemic therapy response, in order to develop novel combination treatments to prevent or delay FGFR3 inhibitor resistance.

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