Downloaded from http://cshperspectives.cshlp.org/ on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Histone Modifications and Cancer James E. Audia1 and Robert M. Campbell2 1Constellation Pharmaceuticals, Cambridge, Massachusetts 02142; 2Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285 Correspondence:
[email protected] SUMMARY Histone posttranslational modifications represent a versatile set of epigenetic marks involved not only in dynamic cellular processes, such as transcription and DNA repair, but also in the stable maintenance of repressive chromatin. In this article, we review many of the key and newly identified histone modifi- cations known to be deregulated in cancer and how this impacts function. The latter part of the article addresses the challenges and current status of the epigenetic drug development process as it applies to cancer therapeutics. Outline 1 Introduction 3 Drug-discovery challenges for histone- modifying targets 2 Histone modifications References Editors: C. David Allis, Marie-Laure Caparros, Thomas Jenuwein, Danny Reinberg, and Monika Lachner Additional Perspectives on Epigenetics available at www.cshperspectives.org Copyright # 2016 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a019521 Cite this article as Cold Spring Harb Perspect Biol 2016;8:a019521 1 Downloaded from http://cshperspectives.cshlp.org/ on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press J.E. Audia and R.M. Campbell OVERVIEW Cancer is a diverse collection of diseases characterized by the Collectively, the combination of histone marks found in dysregulation of important pathways that control normal cel- a localized region of chromatin function through multiple lular homeostasis. This escape from normal control mecha- mechanisms as part of a “chromatin-based signaling” system nisms leads to the six hallmarks of cancer, which include (Jenuwein and Allis 2001; Schreiber and Bradley 2002).