Epigenetic drugs for cancer treatment and prevention: mechanisms of action

Biomolecular Concepts

Yu Xiao-Dan¹  Guo Z. Sheng² 

[1] Department of Pathology, Institute of Basic Medical Sciences, Beijing 100850, China;University of Pittsburgh Cancer Institute and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA;

关键词: cell death;    dna methylation;    drug;    epigenetic therapy;    gene expression;    histone acetylation;    histone methylation;   

DOI  :  10.1515/bmc.2010.020

来源: DOAJ

【 摘 要 】

This review provides a brief overview of the basic principles of epigenetic gene regulation and then focuses on recent development of epigenetic drugs for cancer treatment and prevention with an emphasis on the molecular mechanisms of action. The approved epigenetic drugs are either inhibitors of DNA methyltransferases or histone deacetylases (HDACs). Future epigenetic drugs could include inhibitors for histone methyltransferases and histone demethylases and other epigenetic enzymes. Epigenetic drugs often function in two separate yet interrelated ways. First, as epigenetic drugs per se, they modulate the epigenomes of premalignant and malignant cells to reverse deregulated epigenetic mechanisms, leading to an effective therapeutic strategy (epigenetic therapy). Second, HDACs and other epigenetic enzymes also target non-histone proteins that have regulatory roles in cell proliferation, migration and cell death. Through these processes, these drugs induce cancer cell growth arrest, cell differentiation, inhibition of tumor angiogenesis, or cell death via apoptosis, necrosis, autophagy or mitotic catastrophe (chemotherapy). As they modulate genes which lead to enhanced chemosensitivity, immunogenicity or dampened innate antiviral response of cancer cells, epigenetic drugs often show better efficacy when combined with chemotherapy, immunotherapy or oncolytic virotherapy. In chemoprevention, dietary phytochemicals such as epigallocatechin-3-gallate and sulforaphane act as epigenetic agents and show efficacy by targeting both cancer cells and the tumor microenvironment. Further understanding of how epigenetic mechanisms function in carcinogenesis and cancer progression as well as in normal physiology will enable us to establish a new paradigm for intelligent drug design in the treatment and prevention of cancer.

【 授权许可】

Unknown