Histone deacetylases and their potential as targets to enhance tumour radiosensitisation

Jennifer Antrobus, Jason Parsons*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Downloads (Pure)

Abstract

In mammalian cells, genomic DNA is packaged with histone proteins and condensed into chromatin. To gain access to the DNA, chromatin remodelling is required that is enhanced through histone post-translational modifications, which subsequently stimulate processes including DNA repair and transcription. Histone acetylation is one of the most well understood modifications and is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). These enzymes play critical roles in normal cellular functioning, and the dysregulation of HDAC expression in particular has been linked with the development of a number of different cancer types. Conversely, tumour cell killing following radiotherapy is triggered through DNA damage and HDACs can help co-ordinate the cellular DNA damage response which promotes radioresistance. Consequently, HDAC inhibitors have been investigated as potential radiosensitizers in vitro and in vivo to improve the efficacy or radiotherapy in specific tumour types. In this review, we provide an up-to-date summary of HDACs and their cellular functions, including in DNA damage repair. We also review evidence demonstrating that HDAC inhibitors can effectively enhance tumour radiosensitisation, and which therefore show potential for translation into the clinic for cancer patient benefit.
Original languageEnglish
Pages (from-to)149-167
Number of pages19
JournalRadiation
Volume2
Issue number1
DOIs
Publication statusPublished - 18 Mar 2022

Keywords

  • DNA damage
  • DNA repair
  • HDAC
  • histone deacetylation
  • ionizing radiation
  • photons
  • proton beam therapy

Fingerprint

Dive into the research topics of 'Histone deacetylases and their potential as targets to enhance tumour radiosensitisation'. Together they form a unique fingerprint.

Cite this