Switching off Cancer: Is There a Role for Epigenetics?

摘要

Epigenetics is the study of heritable changes in gene expression that do not involve any change in DNA sequence and include methylation, histone modifications, and altered miRNA or lncRNA expression [1]. Aberrant methylation is a widespread feature in cancer that can lead to transcriptional repression of genes, which is functionally equivalent to the physical deletion of the associated gene(s). Additionally, altered expression of miRNAs and lncRNAs is common in cancer, but the consequences of this are varied and are highly dependent on the target genes regulated [2,3]. Epigenetic mechanisms of gene regulation hold a great deal of promise for cancer therapeutics, as targeting these mechanisms may provide avenues to turn oncogenes “off” or to use demethylating agents to turn tumor suppressor genes back “on”. Additionally, epigenetics holds promise for noninvasive tools to aid cancer diagnosis and inform patient prognosis because these biomarkers (methylated DNA, miRNAs, lncRNAs) are inherently stable, offering greater accessibility in formalin-fixed paraffin-embedded (FFPE) tissues and blood, ensuring minimal disruption to standard clinical practices. However, despite the rising interest and research into epigenetics in cancer, a significant clinical benefit from these studies has not been substantiated. This series of 15 articles (seven original articles, eight review articles) by international leaders in the epigenetics field explores epigenetic changes in cancer as biomarkers or potential therapies, as well as those that advance our understanding of the biological and molecular consequences of these alterations in cancer.