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Trends Pharmacol Sci. 2014 Mar;35(3):136-45. doi: 10.1016/j.tips.2014.01.001. Epub 2014 Feb 12.

Exploiting epigenetic vulnerabilities for cancer therapeutics.

Author information

1
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. Electronic address: skubicek@cemm.oeaw.ac.at.
3
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. Electronic address: snijman@cemm.oeaw.ac.at.

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.

KEYWORDS:

chromatin-modifying enzymes; drugs; non-oncogene addiction; synthetic lethality; therapeutics

PMID:
24529765
DOI:
10.1016/j.tips.2014.01.001
[Indexed for MEDLINE]

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