Epigenetic mechanisms and therapeutic targets of chemotherapy resistance in epithelial ovarian cancer

Ann Med. 2015;47(5):359-69. doi: 10.3109/07853890.2015.1043140. Epub 2015 Jul 10.

Abstract

Epithelial ovarian cancer is the most lethal gynaecological cancer with the majority of patients succumbing to chemotherapy-resistant disease. Unravelling the mechanisms of drug resistance and how it can be prevented or reversed is a pivotal challenge in the treatment of cancer. Epigenetic mechanisms appear to play a crucial role in the development of inherent and acquired resistance in ovarian cancer. Aberrant epigenetic states can be reversed by drug therapy, and thus maintenance of epigenetic change is a potential target to halt or reverse chemotherapy resistance. This review explores the evidence that demonstrates that DNA methylation, histone modification, and microRNAs are associated with inherent and acquired chemotherapy resistance in ovarian cancer and the current challenges associated with this. We also explore current epigenetic therapies used in patients with drug-resistant ovarian cancer and future potential targets.

Keywords: Chemotherapy resistance; DNA methylation; epigenetics; histone modification; microRNA; ovarian cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • DNA Methylation
  • Drug Resistance, Neoplasm / genetics*
  • Epigenesis, Genetic*
  • Female
  • Histones / chemistry
  • Humans
  • MicroRNAs / genetics
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*

Substances

  • Antineoplastic Agents
  • Histones
  • MicroRNAs