Histone deacetylase inhibitors providing an epigenetic treatment in cancer

Abstract

Cancer is among the leading causes of death worldwide and is therefore one of the diseases in which there have been major medical advances and which is the focus of researchers. Drugs used in cancer treatment affect rapidly proliferating normal cells as well as cancer cells. In recent years, targeted therapy has been provided by identifying specific pathways in cancer cells. Epigenetic mechanisms are among the targeted therapies in cancer treatment. Epigenetic regulators ensure the continuity of the normal process by inducing epigenetic changes through epigenetic mechanisms such as DNA methylation, histone post-translational modifications, and non-coding RNA regulation. Histone deacetylases (HDACs), which are involved in transcription-independent events such as DNA repair and mitosis, are enzymes that remove acetyl groups attached to the lysine residue in the amino terminal tails of histones. Histone deacetylase inhibitors (HDACIs) that provide epigenetic treatment of cancer, which play a key role in the balance between acetylation and deacetylation of histone, have been extensively studied by researchers. Today, there are four HDACIs on the market approved by the FDA (Food and Drug Administration) and combinations of these drugs with agents that show anticancer activity by different mechanisms are being studied. Promising results have been obtained from these combinations, and further studies are ongoing on hybrid derivatives of certain HDACIs in various stages.