Epigenetic therapy of cancer with histone deacetylase inhibitors.

摘要: Epigenetics is the study of heritable alterations in gene expression that are not accompanied by corresponding change DNA sequence. Three interlinked epigenetic processes regulate at level chromatin, namely methylation, nucleosomal remodeling and histone covalent modifications. Post-translational modifications occur on certain amino acid residues tails proteins modify chromatin structure form basis for "histone code". The enzymes Histone Acetyl Transferase (HAT) Deacetylase (HDAC) control acetylation histones thereby alter expression. In many cancers, balance between HAT HDAC altered. grouped into four different classes Class I (HDAC1, HDAC2, HDAC3, HDAC8), II (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, HDAC10), III IV (HDAC11). Inhibitors (HDACI) exert anticancer activity promoting as well non-histone protein substrates. effects HDACI transcription complex. They cause cell cycle arrest, inhibit repair, induce apoptosis acetylate non causing downstream a diverse group compounds, which vary structure, biological activity, specificity. general, HDACIs contain zinc-binding domain, capping group, straight chain linker connecting two. classified short fatty acids, hydroxamic cyclic peptides synthetic benzamides. This review describes clinical utility monotherapy combination therapy with other treatment modalities such chemotherapy radiotherapy. Adverse shortcomings also discussed detail.