Epigenetic crosstalk between the tumor microenvironment and ovarian cancer cells: A therapeutic road less traveled

Yuliya Klymenko, Kenneth P. Nephew

Research output: Contribution to journalReview article

10 Scopus citations

Abstract

Metastatic dissemination of epithelial ovarian cancer (EOC) predominantly occurs through direct cell shedding from the primary tumor into the intra-abdominal cavity that is filled with malignant ascitic effusions. Facilitated by the fluid flow, cells distribute throughout the cavity, broadly seed and invade through peritoneal lining, and resume secondary tumor growth in abdominal and pelvic organs. At all steps of this unique metastatic process, cancer cells exist within a multidimensional tumor microenvironment consisting of intraperitoneally residing cancerreprogramed fibroblasts, adipose, immune, mesenchymal stem, mesothelial, and vascular cells that exert miscellaneous bioactive molecules into malignant ascites and contribute to EOC progression and metastasis via distinct molecular mechanisms and epigenetic dysregulation. This review outlines basic epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulators, and summarizes current knowledge on reciprocal interactions between each participant of the EOC cellular milieu and tumor cells in the context of aberrant epigenetic crosstalk. Promising research directions and potential therapeutic strategies that may encompass epigenetic tailoring as a component of complex EOC treatment are discussed.

Original languageEnglish (US)
Article number295
JournalCancers
Volume10
Issue number9
DOIs
StatePublished - Sep 2018

Keywords

  • Chromatin remodeling
  • DNA methylation
  • Epigenetics
  • Histone modifications
  • Non-coding RNAs
  • Ovarian cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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