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.
Authors: Tewodros Mamo; Ann C Mladek; Kris L Shogren; Carl Gustafson; Shiv K Gupta; Scott M Riester; Avudaiappan Maran; Mario Galindo; Andre J van Wijnen; Jann N Sarkaria; Michael J Yaszemski Journal: Biochem Biophys Res Commun Date: 2017-03-12 Impact factor: 3.575
Authors: Amanda R King; Christopher D Corso; Evan M Chen; Eric Song; Paul Bongiorni; Zhe Chen; Ranjini K Sundaram; Ranjit S Bindra; W Mark Saltzman Journal: Mol Cancer Ther Date: 2017-05-31 Impact factor: 6.261
Authors: Roberto Gomez-Casal; Chitralekha Bhattacharya; Michael W Epperly; Per H Basse; Hong Wang; Xinhui Wang; David A Proia; Joel S Greenberger; Mark A Socinski; Vera Levina Journal: Cancers (Basel) Date: 2015-05-22 Impact factor: 6.639
Authors: Rebecca Lamb; Marco Fiorillo; Amy Chadwick; Bela Ozsvari; Kimberly J Reeves; Duncan L Smith; Robert B Clarke; Sacha J Howell; Anna Rita Cappello; Ubaldo E Martinez-Outschoorn; Maria Peiris-Pagès; Federica Sotgia; Michael P Lisanti Journal: Oncotarget Date: 2015-06-10