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 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.
Department of Oncology, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
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Groselj
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Sharma
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Hamdy
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Kerr
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Kiltie
D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D056572:Histone Deacetylase Inhibitors; D011838:Radiation-Sensitizing Agents