Inhibitiors of the adaptor protein Menin are evolving as a novel class of drugs in acute leukemia with the potential to become the first targeted therapeutics that promise a curative treatment. Despite impressive clinical activity in phase-1 clinical trials, disease persistence has been observed leading to resistance development in some patients. In this project, the team will characterize molecular signatures underlying disease persistence during Menin-inhibition and investigate how specific epigenetic regulators re-program leukemia cells towards a “persister-state”. Understanding those processes will help to design rational epigenetic combination therapy approaches to overcome persistence and may facilitate disease eradication in a larger number of patients in the near future.

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