Articles

Changes in epigenetics are key in cancer onset, progression, and therapeutic resistance through balancing the expression of genes without mutating the DNA sequence. In contrast to the non-reversible genetic mutations, the epigenetic changes are dynamic and can possibly be reversed; thus, they offer attractive targets for clinical approaches. This phenomenon is a review of the key epigenetic events in oncogenesis, such as DNA methylation, histone changes, chromatin remodeling, and control by non-coding RNA. Another effect is the silencing of tumor suppressor genes by aberrant promoter hypermethylation and a global hypomethylation that causes genomic instability and the oncogenic activation of oncogenes. The transcriptional control is further interfered with by dysregulation of histone-modifying enzymes and chromatin remodeling complexes, which promote malignant transformation, metastasis, and avoidance of immunity. There is also an emerging body of evidence that highlights the interplay between the reprogramming of epigenetics and the tumor microenvironment, which includes hypoxia, inflammation, and metabolic stress, all of which together influence tumor behavior. Recent developments in high-throughput sequencing and single-cell epigenomics have enhanced the discovery of epigenetic biomarkers, including circulating tumor DNA methylation biomarkers and non-coding RNA biomarkers, to detect and prognose early. Epigenetic-targeted agents, such as DNA methyltransferase and histone deacetylase inhibitors, and new chromatin-modifying enzyme inhibitors have demonstrated clinical utility, at least in hematologic malignancies, and are under investigation with immunotherapy and chemotherapy.