Epigenetic cancer therapies: DNA methyltransferase inhibitors

Expert Opin Investig Drugs. 2002 Jun;11(6):747-54. doi: 10.1517/13543784.11.6.747.

Abstract

Human cancers frequently show altered patterns of DNA methylation, particularly at CpG islands. These CpG islands are sequences of DNA rich in CpG dinucleotides and are often found close to gene promoters. Methylation within islands has been shown to be associated with transcriptional repression of the linked gene. Genes involved in all facets of tumour development and progression can become methylated and epigenetically silenced. Re-expression of such silenced genes can lead to suppression of tumour growth or sensitisation to anticancer therapies. Agents that can reverse DNA methylation include nucleoside and non-nucleoside inhibitors of DNA methyltransferase. Such agents are now undergoing preclinical evaluation and clinical trials in cancer patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • CpG Islands / drug effects
  • DNA Methylation / drug effects*
  • DNA Modification Methylases / antagonists & inhibitors*
  • Humans
  • Neoplasms / classification
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Transcription, Genetic / drug effects

Substances

  • Antineoplastic Agents
  • DNA Modification Methylases