Epigenetic changes in cancer as potential targets for prophylaxis and maintenance therapy

Kirsten Grønbaek, Marianne Treppendahl, Fazila Asmar, Per Guldberg

Abstract

Epigenetic silencing of gene transcription by methylation of DNA or modification of histones is a key event in neoplastic initiation and progression. Alterations of the epigenome have been identified in virtually all types of cancer and involve multiple genes and molecular pathways. Recent studies have suggested that epigenetic gene inactivation may represent the first step in tumorigenesis, possibly by affecting the normal differentiation of stem cells and by predisposing these cells to additional oncogenic insults. The mechanisms that drive epigenetic silencing in pre-malignant cells are still unknown, but may reflect simple stochastic events that are beneficial to cancer precursor cells. It is now well established that epigenetically silenced genes may be reactivated pharmacologically. Some inhibitors of DNA methyltransferases (5-aza-cytidine and 5-aza-2'-deoxycytidine) or histone deacetylases (vorinostat) have been approved for clinical use by the US Food and Drug Administration and have reached clinical phase III trials elsewhere. The prospect that epigenetic alterations may play an essential role in renewing and maintaining the malignant clone has opened up new perspectives for the use of epigenetic therapy in cancer prevention and maintenance.

Original languageEnglish
JournalBasic & clinical pharmacology & toxicology
Volume103
Issue number5
Pages (from-to)389-96
Number of pages8
ISSN1742-7843
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Keywords

  • Antineoplastic Agents/pharmacology
  • Clinical Trials as Topic
  • DNA Methylation/drug effects
  • Drug Delivery Systems
  • Gene Expression Regulation, Neoplastic/drug effects
  • Gene Silencing/drug effects
  • Histones/metabolism
  • Humans
  • Neoplasms/drug therapy
  • Transcription, Genetic

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