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.