Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy

J Cell Mol Med. 2016 Apr;20(4):581-93. doi: 10.1111/jcmm.12771. Epub 2016 Jan 22.

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

Keywords: EOC; TH; epithelial ovarian cancer; genetic and epigenetic alterations; molecular targeted treatment; tumoural heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Carcinoma, Ovarian Epithelial
  • Chromosome Aberrations
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic*
  • Female
  • Genetic Heterogeneity*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / diagnosis
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prognosis

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • Neoplasm Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases