NIH R01 · 2024
ETS1-dependent combinatorial control of oncogenic transcription in Notch-activated T-ALL
The discovery of NOTCH1 as the most prevalent oncogene in T-cell acute lymphoblastic leukemia (T-ALL) patients raised hopes for targeted therapy in this cancer. Unfortunately, in clinical trials, the pan-Notch inhibitor GSI caused dose-limiting toxicities, particularly intestinal, due to abrogation of Notch functions. Our idea to meet this challenge stems from Drosophila studies showing that Notch requires co-binding transcriptional factor partners at its response elements to generate cell-type specific gene expression programs. If these “Notch- collaborating” transcription factors are hijacked to help drive Notch-induced T-ALL, then inhibiting them might oppose Notch signals and circumvent…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.