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

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 ther...

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Bibliographic Details
Published in:British journal of cancer 2013-03, Vol.108 (4), p.748-754
Main Authors: Groselj, B, Sharma, N L, Hamdy, F C, Kerr, M, Kiltie, A E
Format: Article
Language:English
Subjects:
631/208/2489/2487/2486
631/337/1427
692/308/2779/109
692/699/67/1059/485
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Cancer therapies
Cell cycle
Cell death
Chromatin
Clinical Trials as Topic
Combined Modality Therapy
DNA damage
DNA Damage - drug effects
DNA methylation
DNA repair
DNA Repair - drug effects
Drug Resistance
Epidemiology
Epigenetics
Gene expression
Histone deacetylase
Histone Deacetylase Inhibitors - therapeutic use
homologous recombination
Humans
Kinases
Medical research
Medical sciences
mini-review
Minireview
Molecular Medicine
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - radiotherapy
Non-homologous end joining
Oncology
Prostate cancer
Proteins
Radiation
Radiation therapy
Radiation-Sensitizing Agents - therapeutic use
Radiotherapy
Signal transduction
Signal Transduction - drug effects
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2013.21