Related Experiment Video
Updated: May 9, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Epigenetic therapy of non-small cell lung cancer using decitabine (5-aza-2'-deoxycytidine)
1Département de Pharmacologie, Centre de Recherche du CHU Sainte-Justine, Université de Montréal , Montreal, QC , Canada.
Abstract:
Epigenetic analysis shows that many genes that suppress malignancy are silenced by aberrant DNA methylation in lung cancer. Many of these genes are interesting targets for reactivation by the inhibitor of DNA methylation, decitabine (5-aza-2'-deoxycytidine, DAC). A pilot study on intense dose DAC showed promising results in patients with metastatic non-small cell lung cancer (NSCLC). However, subsequent clinical studies using low dose DAC were not very effective against NSCLC and interest in this therapy diminished. Recently, interesting responses were observed in a patient with NSCLC following treatment with a combination of the related inhibitor of DNA methylation, 5-azacytidine, and an inhibitor of histone deacetylation. This finding has generated a renewed interest in the epigenetic therapy of lung cancer. Preclinical studies indicate that DAC has remarkable chemotherapeutic potential for tumor therapy. This epigenetic agent has a delayed and prolonged epigenetic action on tumor cells. This delayed action should be taken into consideration in the design and evaluation of clinical studies on DAC. Future research should be directed at finding the optimal dose-schedule of de DAC for the treatment of NSCLC.
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.
Related Concept Videos
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Inhibition of Cdk Activity
Gene Therapy
Treatment Resistant Cancers