Epigenetic Attire in Ovarian Cancer: The Emperor's New Clothes

Cancer Res. 2020 Sep 15;80(18):3775-3785. doi: 10.1158/0008-5472.CAN-19-3837. Epub 2020 May 7.

Abstract

Ovarian cancer is an aggressive epithelial tumor that remains a major cause of cancer morbidity and mortality in women. Epigenetic alterations including DNA methylation and histone modifications are being characterized in ovarian cancer and have been functionally linked to processes involved in tumor initiation, chemotherapy resistance, cancer stem cell survival, and tumor metastasis. The epigenetic traits of cancer cells and of associated tumor microenvironment components have been shown to promote an immunosuppressive tumor milieu. However, DNA methylation and histone modifications are reversible, and therapies targeting the epigenome have been implicated in potential reinvigoration of the antitumor immunity. In this review, we provide an overview specifically of DNA methylation and histone modifications as "clothes of the ovarian cancer genome" in relationship to their functional effects and highlight recent developments in the field. We also address the clinical implications of therapeutic strategies to remove or alter specific articles of genomic "clothing" and restore normal cellular function. As the clothes of the genome continue to be deciphered, we envision that the epigenome will become an important therapeutic target for cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CpG Islands / genetics
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic*
  • Female
  • Genes, BRCA1
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Nicotinamide N-Methyltransferase / antagonists & inhibitors
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy
  • Tumor Microenvironment / genetics*

Substances

  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • Nicotinamide N-Methyltransferase