Epigenetic alterations and cancer: new targets for therapy.
Over the last two decades, preclinical and clinical research has implicated epigenetic alterations in the pathogenesis and progression of cancer. Epigenetic changes, involving both DNA methylation and alterations in chromatin structure, are associated with the inhibition of transcription of key cell regulatory genes that, under normal conditions, control the cell cycle and initiate apoptotic cell death in neoplastic cells. Drugs have been developed with functional effects, including DNA hypomethylation and histone acetylation, that serve to restore the normal transcription of cell regulatory genes (eg, tumor suppressor genes). DNA hypomethylating agents, such as azacitidine (Vidaza), and histone deacetylase inhibitors such as vorinostat (Zolinza) have been approved in the US for the treatment of cancer, reinforcing the importance of these pathways in the biology of this disease. Current research involves combining these classes of agents and identifying new drug targets within the growing family of epigenetic enzymes.
Allen
Andrew
A
Pharmion Corp, 1700 Owens Street, Suite 205, San Francisco, CA 94158, USA. AAllen@pharmion.com
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018849:Controlled Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D016503:Drug Delivery Systems; D004357:Drug Synergism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents; D006655:Histone Deacetylases