Role of histone deacetylase inhibitors in non-neoplastic diseases

Epigenetic dysregulation has been implicated in the development and progression of a variety of human diseases, but epigenetic changes are reversible, and epigenetic enzymes and regulatory proteins can be targeted using small molecules. Histone deacetylase inhibitors (HDACis), as a class of epigenetic drugs, are widely used to treat various cancers and other diseases involving abnormal gene expression. Specially, HDACis have emerged as a promising strategy to enhance the therapeutic effect of non-neoplastic conditions, including neurological disorders, cardiovascular diseases, renal diseases, autoimmune diseases, inflammatory diseases, infectious diseases and rare diseases, along with their related mechanisms. However, their clinical efficacy has been limited by drug resistance and toxicity. To date, most clinical trials of HDAC inhibitors have been related to the treatment of cancer rather than the treatment of non-cancer diseases, for which experimental studies are gradually underway. Discussions regarding non-neoplastic diseases often concentrate on specific disease types. Therefore, this review highlights the development of HDACis and their potential therapeutic applications in non-neoplastic diseases, either as monotherapy or in combination with other drugs or therapies.