DNA methyltransferase inhibitors for cancer therapy

Cancer J. Jan-Feb 2007;13(1):17-22. doi: 10.1097/PPO.0b013e31803c7245.


Aberrant DNA methylation patterns, including hypermethylation of tumor suppressor genes, have been described in many human cancers. These epigenetic mutations can be reversed by DNA methyltransferase inhibitors, which provide novel opportunities for cancer therapy. Clinical concepts for epigenetic therapies are currently being developed by using azanucleosides for the treatment of leukemias and other tumors. These trials will greatly benefit from the inclusion of molecular markers for monitoring epigenetic changes in patients and for maximizing biologic responses. In addition, novel inhibitors need to be developed that result in a direct and specific inhibition of DNA methyltransferase activity. Several recent developments indicate that rational design of small molecule DNA methyltransferase inhibitors is feasible and that this approach can result in the establishment of novel drug candidates. The use of novel DNA methyltransferase inhibitors in clinical trials that allow monitoring of drug-induced DNA methylation changes should provide the foundation for improved epigenetic cancer therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Azacitidine / analogs & derivatives
  • Azacitidine / therapeutic use
  • DNA Methylation / drug effects
  • DNA Modification Methylases / antagonists & inhibitors*
  • Decitabine
  • Enzyme Inhibitors / therapeutic use*
  • Epigenesis, Genetic / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Decitabine
  • DNA Modification Methylases
  • Azacitidine