Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair.
Br J Cancer
; 108(4): 748-54, 2013 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-23361058
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
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Dano ao DNA
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Reparo do DNA
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Inibidores de Histona Desacetilases
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Neoplasias
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article