Kurzfassung

Drugs targeting epigenetic modifications are very promising therapies in Acute Myeloid Leukemia (AML). However, early clinical trials with compounds targeting epigenetic modifiers as single agents suggest considerable non-genetic resistance, anticipatory combination treatments becoming pivotal for better and longer disease responses. Using models of immediate and late dynamics of epigenetic and transcriptional adaptations after inhibition of the crucial regulators of transcription bromodomain...Drugs targeting epigenetic modifications are very promising therapies in Acute Myeloid Leukemia (AML). However, early clinical trials with compounds targeting epigenetic modifiers as single agents suggest considerable non-genetic resistance, anticipatory combination treatments becoming pivotal for better and longer disease responses. Using models of immediate and late dynamics of epigenetic and transcriptional adaptations after inhibition of the crucial regulators of transcription bromodomain and extraterminal (BET) proteins, we propose to discover how and why AML cells develop resistance to BET inhibition, how to prevent the emergence of BET inhibition resistance and if the hereby derived models can be used as a paradigm for other epigenetic/transcriptional modulators.» weiterlesen» einklappen