alexa Exploiting epigenetic vulnerabilities for cancer therapeutics.
Immunology

Immunology

Immunotherapy: Open Access

Author(s): Mair B, Kubicek S, Nijman SM, Mair B, Kubicek S, Nijman SM, Mair B, Kubicek S, Nijman SM, Mair B, Kubicek S, Nijman SM

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Abstract Epigenetic deregulation is a hallmark of cancer, and there has been increasing interest in therapeutics that target chromatin-modifying enzymes and other epigenetic regulators. The rationale for applying epigenetic drugs to treat cancer is twofold. First, epigenetic changes are reversible, and drugs could therefore be used to restore the normal (healthy) epigenetic landscape. However, it is unclear whether drugs can faithfully restore the precancerous epigenetic state. Second, chromatin regulators are often mutated in cancer, making them attractive drug targets. However, in most instances it is unknown whether cancer cells are addicted to these mutated chromatin proteins, or whether their mutation merely results in epigenetic instability conducive to the selection of secondary aberrations. An alternative incentive for targeting chromatin regulators is the exploitation of cancer-specific vulnerabilities, including synthetic lethality, caused by epigenetic deregulation. We review evidence for the hypothesis that mechanisms other than oncogene addiction are a basis for the application of epigenetic drugs, and propose future research directions. Copyright © 2014 Elsevier Ltd. All rights reserved. This article was published in Trends Pharmacol Sci and referenced in Immunotherapy: Open Access

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