Histone deacetylase inhibitors as radiosensitisers: Effects on DNA damage signalling and repair

B. Groselj, N. L. Sharma, F. C. Hamdy, M. Kerr, A. E. Kiltie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

Many cancers display increased expression of histone deacetylases (HDACs) and therefore transcriptionally inactive chromatin, resulting in the downregulation of genes including tumour suppressor and DNA repair genes. Histone deacetylase inhibitors (HDACi) are a heterogeneous group of epigenetic therapeutics, showing promising anticancer effects in both pre-clinical and clinical settings, in particular the effect of radiosensitisation when administered in combination with radiotherapy. Radiotherapy remains one of the most common forms of cancer treatment, leading to cell death through the induction of DNA double-strand breaks (DSBs). Cells have developed mechanisms to repair such DSB through two major pathways: non-homologous end-joining and homologous recombination. Here, we explore the current evidence for the use of HDACi in combination with irradiation, focusing on the effects of HDACi on DNA damage signalling and repair in vitro. In addition, we summarise the clinical evidence for using HDACi with radiotherapy, a growing area of interest with great potential clinical utility.

Original languageEnglish
Pages (from-to)748-754
Number of pages7
JournalBritish Journal of Cancer
Volume108
Issue number4
DOIs
Publication statusPublished - 5 Mar 2013

Keywords

  • clinical trials
  • DNA damage signalling
  • DNA repair
  • histone deacetylase inhibitors

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