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Histone deacetylase inhibitors: discovery and development as anticancer agents

2005; Taylor & Francis; Volume: 14; Issue: 12 Linguagem: Inglês

10.1517/13543784.14.12.1497

1744-7658

Paul A. Marks, Milos Dokmanovic,

Nuclear Receptors and Signaling

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.