Epigenetic Therapies

  • Robert Brown
  • Nadine Chapman-Rothe
  • Ros Glasspool
Chapter

Abstract

Epigenetic mechanisms lead to an alteration in gene expression that is maintained through cell division, but does not involve a change in DNA sequence. Such epigenetic mechanisms include DNA methylation, post-translational modifications of histones and non-coding RNAs. All types of ovarian cancer show wide-spread aberrant epigenetic changes, leading to changes in expression of genes involved in all the hallmarks of cancer, as well as genes involved in how tumours will respond to chemotherapy. Such epimutations can be reversed using small molecule inhibitors of maintenance of the epigenetic state. Demethylating agents and histone deacetylase inhibitors have shown activity against certain haematological malignancies, however their activity in solid tumours remains more uncertain. Major challenges remain in the delivery of epigenetic therapy, the maintenance of a pharmacodynamic response and the achievement of a clear therapeutic index. In addition, the development of robust predictive biomarkers linked to an understanding of the underlying biology will be key to improved epigenetic therapy approaches. Defining the epigenetic alongside the genetic landscape of individual ovarian cancer subtypes should allow epigenetic therapy to be targeted to those groups of patients who are most likely to benefit from this treatment.

Keywords

DNMT HDAC Epigenetic DNA methylation 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Robert Brown
    • 1
  • Nadine Chapman-Rothe
    • 1
  • Ros Glasspool
    • 2
  1. 1.Epigenetics Unit, Department of Surgery and CancerImperial College London, Hammersmith HospitalLondonUK
  2. 2.Beatson Oncology Centre, The Beatson West of Scotland Cancer CentreGlasgowUK

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