Epigenetics in Cancer Biology

Abstract

The term epigenetics dates back to the 1940s, when Conrad Waddington introduced it to refer to gene expression changes that occur during development and do not involve alterations in the DNA sequence. Subsequently the definition expanded beyond development, and the field became one of the most rapidly developing ones in life sciences. Advances in epigenetics transformed our understanding of cellular and molecular events that occur during development, homeostasis, and disease and helped explain processes that have long fascinated and puzzled scientists, such as the link between inflammation and disease, the intricacies of memory formation and maintenance, and the connection between the social environment/social adversity and chronic disease risk. Epigenetically mediated gene expression changes were described in a broad group of medical conditions, including cancer and neurodegenerative, metabolic, autoimmune, psychiatric, and cardiovascular diseases and, of these, the most advanced understanding of their contribution, so far, has occurred for cancer. Changes in DNA methylation, histone posttranslational modifications, and microRNA alterations, described in a broad group of human cancers, were implicated in all stages of carcinogenesis, including initiation, progression, invasion, and metastasis. The discovery of epigenetic biomarkers facilitated novel strategies for the early detection of disease, helped better monitor progression, therapeutic response, and prognosis, and revolutionized personalized medicine. Moreover, the reversible nature of epigenetic marks opened the possibility to therapeutically reverse aberrant gene expression patterns and catalyzed the emergence of epigenetic drugs. Besides their promise as monotherapies, epigenetic drugs show considerable interest thanks to the possibility to combine them with other cancer therapeutic modalities, such as chemotherapy, hormone therapy, and radiation therapy.