Pharmacological inhibition of histone deacetylases for the treatment of cancer, neurodegenerative disorders and inflammatory diseases

Expert Opin Drug Discov. 2008 Sep;3(9):1041-65. doi: 10.1517/17460441.3.9.1041.

Abstract

Background: Histone deacetylases (HDACs) constitute a family of enzymes that deacetylate histones and other cellular proteins. They are major regulators of transcription and are also important in other cellular processes.

Objective: The review provides an updated summary of HDAC pharmacological inhibition in clinical oncology, as well as in preclinical studies on inflammation and neurodegenerative diseases.

Results/conclusion: HDAC inhibition is a validated approach in cancer therapy, as evidenced by the approval of vorinostat and by encouraging clinical data from various HDAC inhibitors. Moreover, preclinical proof-of-concept studies are emerging from animal models for non-oncologic diseases, including inflammatory and neurodegenerative diseases. The identification of the appropriate target spectrum and the development of class- or isotype-selective inhibitors will be central events in the future.