Investigating drug response and resistance to IDH1R132H inhibition and hypomethylating agents in AML

Abstract

Mutations in epigenetic regulators frequently occur in AML. Furthermore, the epigenetic landscape is typically dysregulated in AML. Targeted epigenetic therapeutics that directly inhibit mutant epigenetic oncogenic drivers, such as AG120 inhibition of IDH1R132H, have shown clinical success for the treatment of IDH1-mutant AML. Other epigenetic therapies target wildtype epigenetic regulators, such as DNMT1 inhibition by hypomethylating agents, with the aim of reprogramming the transcriptional networks driving malignant progression. Despite some patients achieving clinical remission, many AML patients do not respond to epigenetic therapies or relapse post-treatment. Furthermore, the contributi..