Histone deacetylase inhibitors: discovery and development as anticancer agents.
Histone deacetylase (HDAC) inhibitors are a new class of targeted anticancer agents. Several HDAC inhibitors are in clinical trials and have shown significant activity against a spectrum of both haematological and solid tumours at doses that are well tolerated by patients. HDACs and histone acetyltransferases can, by reversible acetylation, modify the structure and function of histones and proteins in transcription factor complexes, which are involved in the regulation of gene expression, as well as many non-histone proteins that are involved in regulating cell proliferation and cell death. HDAC inhibitors are a structurally diverse group of molecules; these agents selectively alter the expression of genes. HDAC inhibitors can induce cancer cell death, whereas normal cells are relatively resistant to HDAC inhibitor-induced cell death.
Marks
Paul A
PA
Memorial Sloan-Kettering Cancer Center, Cell Biology Program, Sloan-Kettering Institute for Cancer Research, New York City, New York 10021, USA. marksp@mskcc.org
Dokmanovic
Milos
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors