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.
Source: Histone deacetylase inhibitors
as radiosensitisers: effects on DNA damage signalling and repair. Groselj B,
Sharma NL, Hamdy FC, Kerr M, Kiltie AE (anne.kiltie@oncology.ox.ac.uk).
Br J Cancer. 2013 Jan 29.
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