DNA-dependent protein kinase and its inhibition in support of radiotherapy.

Eva Novotná, Aleš Tichý, Jaroslav Pejchal, Emílie Lukášová, Barbora Salovská, Jiřina Vávrová

Department of Radiation Biology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic.

International journal of radiation biology 2013 Jun

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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. 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.

Citation

Eva Novotná, Aleš Tichý, Jaroslav Pejchal, Emílie Lukášová, Barbora Salovská, Jiřina Vávrová. DNA-dependent protein kinase and its inhibition in support of radiotherapy. International journal of radiation biology. 2013 Jun;89(6):416-23