title: HDACi--going through the mechanisms.
abstract: Histone deacetylases inhibitors (HDACi) have recently emerged as potent antitumor treatment modality. They are currently tested in many phase I, II and III clinical trials as single agents as wells as in combination schemes. They have demonstrated promising antitumor activity and favorable clinical outcome. Histone deacetylases (HDACs) are involved in the process of epigenetic regulation of gene expression. Epigenetic changes are believed to be crucial for the onset and progression of cancer and have recently gained remarkable attention. Since epigenetic regulation of gene expression is a reversible process, targeting histone deacetylases provides a good rationale for anticancer therapy. The acetylation status of histones regulates the organization of chromatin and the access of transcription factors. Moreover, functions of many non-histone proteins are controlled by acetylation. The broad and complicated influences of HDACi on various molecular processes may account for the observed pleiotropic effects. In this review we summarize recent advances in the understanding of biology of HDACs and mechanism of action of their inhibitors.
authors.affiliation: Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1A, F building, 02-097 Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wanczyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Roszczenko
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Marcinkiewicz
authors.forename: Kamil
authors.initials: K
authors.lastname: Bojarczuk
authors.forename: Michal
authors.initials: M
authors.lastname: Kowara
authors.forename: Magdalena
authors.initials: M
authors.lastname: Winiarska
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D045643:DNA Repair Enzymes / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D009687:Nuclear Proteins / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006655:Histone Deacetylases; D045643:DNA Repair Enzymes