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The Cancer Epigenome

Can it be Targeted for Therapy?

  • Chapter
Molecular Targeting in Oncology

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Summary

It has become increasingly clear in recent years that reversible alterations in the epigenome, which comprises the chromatin terrain and determines individual gene expression, has as great a role in defining the normal or malignant phenotype of a cell as does the more-familiar fixed genomic DNA sequence upon which it is superimposed. The “epigenomic code” is defined by DNA methylation patterns, unique combinations of post-translational modifications of histones and non-histone proteins, the nature of the remodeled chromatin structure, and the identity of nucleoprotein complexes assembled on the chromatin. The distinctive epigenomic code associated with each individual gene dictates the expression status of that gene, dependent upon its localization and the associated unique chromatin organization. For example, silencing of gene expression, including silencing of tumor suppressor genes, is associated with local deacetylation of histones, and often localized to genomic regions containing DNA methylation as well as methylation at lysine residues 9 and 27 of histone H3, and lysine residue 20 of histone H4. In contrast, activation of gene expression, including activation of oncogenes, is associated with locally acetylated histones and methylation at lysine residues 4, 36, and 79 of histone H3. Currently, there are two groups of drugs targeting the epigenome: inhibitors of DNA methyl transferases and inhibitors of histone deacetylases. These agents have been employed with some success in pre-clinical studies and in early limited clinical trials. In the long term, the development of therapeutic agents which can target with precision the activities of a wide array of specific chromatin-modifying enzymes may become useful in reversing the epigenomic alterations which define the cancer cell (the cancer epigenome) and provide a novel therapeutic approach to malignancy.

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Authors
  1. Sam Thiagalingam PhD
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  2. Douglas V. Faller MD,PhD
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Editors and Affiliations

  1. Division of Surgical Oncology, Columbia University, New York, NY

    Howard L. Kaufman

  2. Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College Cornell University, New York, NY

    Scott Wadler

  3. Boston University Medical Campus Boston University School of Medicine, Boston, MA

    Karen Antman

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Thiagalingam, S., Faller, D.V. (2008). The Cancer Epigenome. In: Kaufman, H.L., Wadler, S., Antman, K. (eds) Molecular Targeting in Oncology. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-337-0_5

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  • DOI: https://doi.org/10.1007/978-1-59745-337-0_5

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