Medical epigenetics is a science of studying various diseases through epigenetics, in which gene expression and gene function change heritably and eventually lead to phenotypic change without the change of DNA sequence. Epigenetic modification mainly includes DNA methylation, histone modification, and noncoding RNA regulation, which play important roles in gene-selective transcription and posttranscriptional regulation. Here, we will focus on introducing prospective advances of DNA methylation, as well as histone modification and noncoding RNA regulation in medical epigenetics, so as to provide a more comprehensive and specific understanding of the pathogenesis of diseases, and also provide scientific basis for clinical diagnosis and development of therapeutic drugs.
The majority of solid tumors harbor disrupted epigenomes that contribute to malignancy. Over the past decade, there has been a substantial increase in our understanding of the epigenetic mechanisms underlying normal and disease states. Profiling of tumors revealed recurrent mutations in key components of the epigenetic machinery and metabolic enzymes that lead to an altered epigenetic state and oncogenic transformation. Unlike genetic events, epigenetic alterations can be targeted pharmacologically and potentially reversed. Drug discovery efforts are focused on developing epigenetic drugs and treatment regimens. Recently, altered DNA methylation has emerged as an important and promising feature for tumor classification. In this chapter, we highlight recent advances in solid tumor epigenetics, specifically focusing on epigenetic therapies and the most promising combination strategies currently under investigation. In addition, we illustrate the utility of epigenetic markers for solid tumor classification and the emerging field of analyzing epigenetic biomarkers in liquid biopsies.
The newly emerged epigenomic technologies promoted a new discipline called pharmacoepigenomics to identify the epigenomic signatures affecting individual response to drugs. There are multiple layers of epigenomic events, including DNA methylation changes, histone modifications, and microRNA-mediated regulation, which are being studied in the field of neurodegenerative disease (NDD) treatment. To date, the Food and Drug Administration-approved drugs mostly provide symptomatic relief or can be able to delay the progression rather than definitively stop the diseases. Due to the multifactorial nature of these disorders, and the documented individualized response to the same treatments, the attention of researchers has been directed toward pharmacoepigenomics. Several clinical trials are ongoing and the search for effective epigenomic-modifying drugs against NDDs is being undertaken worldwide. This exciting research line might lead to novel approaches in drug discovery and in the individualized and personalized application of drug therapy.
