Epigenetic regulation in cancer

Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. Our review delves into the complexities of epigenetic regulation, exploring its profound effects on tumor initiation, metastatic behavior, metabolic pathways, and the tumor microenvironment. We place a particular emphasis on the dysregulation at each level of epigenetic modulation, including but not limited to, the aberrations in enzymes responsible for DNA methylation and histone modification, subunit loss or fusions in chromatin remodeling complexes, and the disturbances in higher-order chromatin structure. Finally, we also evaluate therapeutic approaches that leverage the growing understanding of chromatin dysregulation, offering new avenues for cancer treatment. Epigenetic alterations can contribute to the acquisition of hallmark capabilities during tumor development and malignant progression. Central to these changes are aberrant DNA methylation patterns, which can silence tumor suppressor genes and activate oncogenes. Histone modifications also influence chromatin structure and gene expression. Furthermore, chromatin remodeling alters the transcriptional regulation of genes, while changes in higher-order chromatin structure may modify the spatial interactions between genes and their regulatory elements. We focus on how these mechanisms impact tumorigenesis, metastasis, metabolic reprogramming, and the tumor microenvironment. # image