DNA-dependent protein kinase and its inhibition in support of radiotherapy.
OBJECTIVE
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.
Department of Radiation Biology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic.
Eva
E
Novotná
Aleš
A
Tichý
Jaroslav
J
Pejchal
Emílie
E
Lukášová
Barbora
B
Salovská
Jiřina
J
Vávrová
D000818:Animals; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects*; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011878:Radiotherapy / Q000379:methods*
D011838:Radiation-Sensitizing Agents; D051747:DNA-Activated Protein Kinase