The epigenome as a target for cancer chemoprevention.
Epigenetic events, a key driving force in the development of cancer, are alterations in gene expression without changes in the DNA coding sequence that are heritable through cell division. Such changes occur throughout all stages of tumorigenesis, including the early phases, and are increasingly recognized as major mechanisms involved in silencing tumor suppressor genes. Epigenetic changes can be reversed by the use of small molecules and, thus, such changes are promising targets for cancer chemopreventive drug development. This review examines the basis for targeting the epigenome as a prevention strategy, focusing on understanding the epigenetic changes that occur before the development of frank malignancy, when chemopreventive intervention will have the maximal impact.
Kopelovich
Levy
L
Chemopreventive Agent Development Research Group, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. kopelovl@mail.nih.gov
Crowell
James A
JA
Fay
Judith R
JR
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015894:Genome, Human; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D008780:Methyltransferases