2022 World Conference on Lung Cancer (ePosters)-EP16.04-021. Chromatin Remodeling Drives Lung Pre-malignancy and is a Target for Prevention

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A recent study conducted by the Lung Cancer Program at the Lovelace Biomedical Research Institute in Albuquerque, NM, examined the role of chromatin remodeling in driving lung premalignancy and its potential as a target for prevention. The researchers focused on the epigenetic deregulation of genes involved in cell regulation, specifically the methylation of cytosine and histone modifications in gene promoters to silence transcription.<br /><br />The study used a human bronchial epithelial (HBEC) premalignancy model and a mouse model to investigate the role of histone modifications in transformation and the effect of targeting specific enzymes involved in these modifications. The researchers found that while methylation was observed in a small number of genes in the HBEC lines, hundreds of genes showed altered expression. Many of these genes became methylated in tumors.<br /><br />The researchers also examined the effect of small molecule inhibitors targeting the enzymes EZH2 and G9a on transformation and transcriptional reprogramming. They found that one inhibitor, DZNep, was able to reverse transformation by 70-80% and induce transcriptional reprogramming. In the mouse model, DZNep treatment prevented the progression of hyperplasia to adenomas by 55%.<br /><br />The findings of this study suggest that targeting EZH2 with DZNep could be an effective strategy for preventing lung cancer. The ability of DZNep to reverse transformation, prevent progression of premalignancy, and induce transcriptional reprogramming highlights its potential as a chemopreventive agent.<br /><br />Overall, this study provides new insights into the role of chromatin remodeling in lung premalignancy and identifies a potential target for prevention. The findings suggest that targeting EZH2 with DZNep could be a promising approach to reduce the risk of developing lung cancer, particularly for former smokers who are still at risk. Further research is needed to validate these findings and explore the translational potential of this approach.

Asset Subtitle

Steven Belinsky

Meta Tag

Speaker Steven Belinsky

Topic Tumour Biology and Biomarkers - Tumour Biology & Preclinical Studies

Keywords

Lung Cancer Program

chromatin remodeling

lung premalignancy

epigenetic deregulation

methylation of cytosine

histone modifications

transcriptional reprogramming

EZH2

DZNep

chemopreventive agent