Epigenetic regulation and cancer (review).

ABSTRACT

'Epigenetics' is defined as the inheritable changes in gene expression with no alterations in DNA sequences. Epigenetics is a rapidly expanding field, and the study of epigenetic regulation in cancer is emerging. Disruption of the epigenome is a fundamental mechanism in cancer, and several epigenetic drugs have been proven to prolong survival and to be less toxic than conventional chemotherapy. Promising results from combination clinical trials with DNA methylation inhibitors and histone deacetylase inhibitors have recently been reported, and data are emerging that describe molecular determinants of clinical responses. Despite significant advances, challenges remain, including a lack of predictive markers, unclear mechanisms of response and resistance, and rare responses in solid tumors. Preclinical studies are ongoing with novel classes of agents that target various components of the epigenetic machinery. In the present review, examples of studies that demonstrate the role of epigenetic regulation in human cancers with the focus on histone modifications and DNA methylation, and the recent clinical and translational data in the epigenetics field that have potential in cancer therapy are discussed.