Targeting Chromatin Modifying Enzymes in Anticancer Drug Discovery

  • Victoria M. Richon
  • Mikel P. Moyer
  • Robert A. Copeland


Over the past decade the sequencing of human cancer genomes has provided a wealth of information on recurrent genetic alterations in specific subsets of cancers. The understanding of the underlying genetic alterations responsible for oncogenesis in these cancers has led to the successful development of new therapies specifically targeting the genetic alterations. The successes so far have come mainly from targeting genetic alterations in kinases. For example, the identification of mutant V600E RAF in melanoma led to the development of the vemurafenib (a BRAF inhibitor) for the subset of melanoma patients containing this mutation (Bollag et al Nat Rev Drug Discov 11(11):873–76, 2012). Likewise, the identification of the EML4-ALK translocation in a subset of non-small cell lung cancer patients led to approval of crizotinib (an ALK inhibitor) in this patient subset (Ou et al Oncologist 17(11):1351–75, 2012). In addition to the identification of kinase driver mutations, these genomic analyses have also identified chromatin modifying enzymes, specifically, enzymes involving protein methylation, as some of the most frequently observed somatic alterations in cancer. This chapter will focus on the protein methyltransferase class of chromatin modifying enzymes, providing the basis for their emergence as high priority targets for cancer drug discovery and the progress made in the development of inhibitors against this class of targets.


Epigenetics Chromatin Histone Methylation Methyltransferase Cancer Genetic alterations Inhibitor 


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Victoria M. Richon
    • 1
  • Mikel P. Moyer
    • 2
  • Robert A. Copeland
    • 2
  1. 1.Oncology Discovery and Preclinical Sciences, Global Oncology Division, SanofiCambridgeUSA
  2. 2.R&D DepartmentEpizyme, Inc.CambridgeUSA

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