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  • PURPOSE: Radiotherapy has been used as a treatment of almost 50% of all malignant tumors. The aim of this review is to provide a comprehensive overview of the recent knowledge in the field of molecular mechanisms of radiation-induced double-stranded breaks (DSB) repair. This paper gives particular emphasis to a key DNA repair enzyme, DNA-dependent protein kinase (DNA-PK), which plays a pivotal role in non-homologous end-joining. Furthermore, we discuss possibilities of DNA-PK inhibition and other molecular approaches employed in order to facilitate radiotherapy. CONCLUSIONS: We have reviewed the recent studies using novel potent and selective small-molecular DNA-PK inhibitors and we conclude that targeted inhibition of DNA repair proteins like DNA-PK in cancer cells, in combination with ionizing radiation, improves the efficacy of cancer therapy while minimizing side-effects of ionizing radiation. Moreover, the recent discovery of short interfering RNA (siRNA) and signal interfering DNA (siDNA)-based therapeutics, or small peptides and RNA, shows a new opportunity of selective and safe application of biological treatment. All of these approaches are believed to contribute to more personalized anti-cancer therapy.
  • PURPOSE: Radiotherapy has been used as a treatment of almost 50% of all malignant tumors. The aim of this review is to provide a comprehensive overview of the recent knowledge in the field of molecular mechanisms of radiation-induced double-stranded breaks (DSB) repair. This paper gives particular emphasis to a key DNA repair enzyme, DNA-dependent protein kinase (DNA-PK), which plays a pivotal role in non-homologous end-joining. Furthermore, we discuss possibilities of DNA-PK inhibition and other molecular approaches employed in order to facilitate radiotherapy. CONCLUSIONS: We have reviewed the recent studies using novel potent and selective small-molecular DNA-PK inhibitors and we conclude that targeted inhibition of DNA repair proteins like DNA-PK in cancer cells, in combination with ionizing radiation, improves the efficacy of cancer therapy while minimizing side-effects of ionizing radiation. Moreover, the recent discovery of short interfering RNA (siRNA) and signal interfering DNA (siDNA)-based therapeutics, or small peptides and RNA, shows a new opportunity of selective and safe application of biological treatment. All of these approaches are believed to contribute to more personalized anti-cancer therapy. (en)
Title
  • DNA-dependent protein kinase and its inhibition in support of radiotherapy
  • DNA-dependent protein kinase and its inhibition in support of radiotherapy (en)
skos:prefLabel
  • DNA-dependent protein kinase and its inhibition in support of radiotherapy
  • DNA-dependent protein kinase and its inhibition in support of radiotherapy (en)
skos:notation
  • RIV/60162694:G44__/13:43874893!RIV14-MO0-G44_____
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, S
http://linked.open...iv/cisloPeriodika
  • 6
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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  • 70159
http://linked.open...ai/riv/idVysledku
  • RIV/60162694:G44__/13:43874893
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • siRNA; small molecule inhibitors; DSB; NHEJ; fractionated irradiation; DNA-PK (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [CAF808C29D9C]
http://linked.open...i/riv/nazevZdroje
  • International Journal of Radiation Biology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 89
http://linked.open...iv/tvurceVysledku
  • Novotná, Eva
  • Pejchal, Jaroslav
  • Tichý, Aleš
  • Vávrová, Jiřina
  • Lukášová, Emílie
  • Šalovská, Barbora
http://linked.open...ain/vavai/riv/wos
  • 000319747500004
issn
  • 0955-3002
number of pages
http://bibframe.org/vocab/doi
  • 10.3109/09553002.2013.767993
http://localhost/t...ganizacniJednotka
  • G44
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