Epigenetic therapy of non-small cell lung cancer using decitabine (5-aza-2'-deoxycytidine)

Richard L Momparler1

  • 1Département de Pharmacologie, Centre de Recherche du CHU Sainte-Justine, Université de Montréal , Montreal, QC , Canada.

Frontiers in Oncology
|August 3, 2013
PubMed

Insights

Decitabine (DAC) shows potential for epigenetic therapy in lung cancer by reactivating silenced tumor suppressor genes. Further research is needed to optimize DAC dosing for effective non-small cell lung cancer treatment.

Area of Science:

  • Oncology
  • Epigenetics
  • Pharmacology

Background:

  • Aberrant DNA methylation silences malignancy-suppressing genes in lung cancer.
  • Decitabine (5-aza-2'-deoxycytidine, DAC), a DNA methylation inhibitor, can potentially reactivate these silenced genes.
  • Previous studies on DAC in non-small cell lung cancer (NSCLC) yielded mixed results, with low doses proving ineffective.

Purpose of the Study:

  • To re-evaluate the potential of epigenetic therapy, specifically using decitabine (DAC), for lung cancer treatment.
  • To highlight the delayed and prolonged action of DAC on tumor cells, which needs consideration in clinical study design.
  • To emphasize the need for further research into optimal DAC dosing and scheduling for NSCLC.

Main Methods:

  • Review of preclinical and clinical studies on decitabine (DAC) in lung cancer.
  • Analysis of epigenetic mechanisms involving DNA methylation and gene silencing in NSCLC.
  • Consideration of combination therapies involving DNA methylation inhibitors.

Main Results:

  • A pilot study with high-dose DAC showed promise in metastatic NSCLC.
  • Low-dose DAC studies were less effective, diminishing interest in this approach.
  • Recent observations of responses with 5-azacytidine (a related compound) and a histone deacetylation inhibitor suggest renewed potential for epigenetic therapy.

Conclusions:

  • Decitabine (DAC) exhibits significant chemotherapeutic potential for lung cancer via epigenetic mechanisms.
  • The delayed and prolonged action of DAC necessitates careful consideration in clinical trial design and evaluation.
  • Optimal dose-scheduling of DAC is crucial for effective NSCLC treatment and requires further investigation.

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