Pathological Role of HDAC8: Cancer and Beyond

Cells. 2022 Oct 9;11(19):3161. doi: 10.3390/cells11193161.


Histone deacetylase 8 (HDAC8) is a class I HDAC that catalyzes the deacetylation of histone and non-histone proteins. As one of the best-characterized isoforms, numerous studies have identified interacting partners of HDAC8 pertaining to diverse molecular mechanisms. Consequently, deregulation and overexpression of HDAC8 give rise to diseases. HDAC8 is especially involved in various aspects of cancer progression, such as cancer cell proliferation, metastasis, immune evasion, and drug resistance. HDAC8 is also associated with the development of non-cancer diseases such as Cornelia de Lange Syndrome (CdLS), infectious diseases, cardiovascular diseases, pulmonary diseases, and myopathy. Therefore, HDAC8 is an attractive therapeutic target and various HDAC8 selective inhibitors (HDAC8is) have been developed. Here, we address the pathological function of HDAC8 in cancer and other diseases, as well as illustrate several HDAC8is that have shown anti-cancer effects.

Keywords: HDAC8; HDAC8 selective inhibitors; cancer; epigenetics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • De Lange Syndrome*
  • Histone Deacetylases / metabolism
  • Humans
  • Neoplasms*
  • Protein Isoforms
  • Repressor Proteins


  • Protein Isoforms
  • Repressor Proteins
  • HDAC8 protein, human
  • Histone Deacetylases

Grants and funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (2018R1A6A1A03023718, 2019R1A2C1008619, and 2019H1A2A1076925) and by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C0952, Republic of Korea).