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Bechter, Oliver; Schöffski, Patrick
Pharmacology & therapeutics (Oxford), April 2020, 2020-04-00, 20200401, Volume: 208Journal Article
Bromodomains are protein-protein interaction modules with a great diversity in terms of number of proteins and their function. The bromodomain and extraterminal protein (BET) represents a distinct subclass of bromodomain proteins mainly involved in transcriptional regulation via their interaction with acetylated chromatin. In cancer cells BET proteins are found to be altered in many ways such as overexpression, mutations and fusions of BET proteins or their interference with cancer relevant signaling pathways and transcriptional programs in order to sustain cancer growth and viability. Blocking BET protein function with small molecules is associated with therapeutic activity. Consequently, a variety of small molecules have been developed and a number of phase I clinical trials have explored their tolerability and efficacy in patients with solid tumors and hematological malignancies. We will review the rational for applying BET inhibitors in the clinic and we will discuss the toxicity profile as well as efficacy of this new class of protein inhibitors. We will also highlight the emerging problem of treatment resistance and the potential these drugs might have when combined with other anti-cancer therapies.
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