Epigenetic marks such as DNA methylation, histone modifications, and non-coding RNAs play a central role in regulating gene expression without altering the DNA sequence. These dynamic and reversible modifications contribute to cellular differentiation, genomic stability, and the fine-tuning of transcriptional activity in response to environmental and metabolic cues. Beyond genetic variation alone, epigenetic mechanisms provide a critical regulatory layer linking environmental factors, cellular context, and disease susceptibility. Alterations in epigenetic marks can disrupt normal gene expression patterns, contributing to a wide range of pathological conditions, including cancer, neurodegenerative, metabolic, and immune-mediated diseases. This review places particular emphasis on cancer, cardiovascular diseases, and autoimmune disorders, where epigenetic dysregulation has been most extensively characterized and therapeutically explored. Because epigenetic modifications are reversible and influenced by environmental and lifestyle factors, they represent highly promising targets for therapeutic intervention. In recent years, epigenetic-based drugs—such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and agents targeting non-coding RNAs—have demonstrated significant potential in preclinical and clinical studies. However, their clinical application remains limited by challenges including non-selectivity, systemic toxicity, and limited tissue specificity. Emerging technologies such as CRISPR/dCas9-mediated epigenome editing offer opportunities for precise regulation of disease-associated genes without permanent genomic alterations. This review summarizes current knowledge on major epigenetic mechanisms and highlights recent advances in epigenetic therapies, including FDA-approved agents, combinatorial strategies, and next-generation epigenetic editing approaches. A deeper understanding of these mechanisms is expected to enable targeted, reversible, and patient-specific therapeutic strategies within the framework of precision medicine.
Kankaya et al. (Tue,) studied this question.