Journal
BRITISH JOURNAL OF CANCER
Volume 108, Issue 4, Pages 748-754Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.21
Keywords
histone deacetylase inhibitors; DNA damage signalling; DNA repair; clinical trials
Categories
Funding
- Medical Research Council [G0900871] Funding Source: Medline
- MRC [G0900871] Funding Source: UKRI
- Medical Research Council [G0900871] Funding Source: researchfish
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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.
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