PMID: 25764827Mar 15, 2015Paper

On the prospects of using the DNA repair inhibitors in radiotherapy of tumors

Radiatsionnaia biologiia, radioecologiia
A I Gaziev

Abstract

The cellular DNA repair systems sufficiently provide the resistance of tumors to ionizing radiation, and thus contribute to reducing the effectiveness of their radiotherapy. Therefore, suppression of the activity of critical DNA repair enzymes in tumor cells is considered one of the promising directions to overcome this resistance. As can be seen from the literature analysis, the use of many inhibitors of DNA repair enzymes have not yet yielded the results, which can be extrapolated to preclinical models or clinical trials. However, experimental studies show that the inhibitors of the enzyme family of poly(ADP-ribose) polymerases (PARP) are able to inhibit the growth of various human tumor cells. Pre-clinical and clinical trials of the PARP inhibitors also show promising results in terms of the possibility of their wide practical application. The effect of the PARP inhibitors consists in the blockage of the most important DNA repair systems. This leads to the accumulation of DNA single-strand breaks, the collapse of replication forks and to generation of lethal double-strand breaks (DSB). The PARP inhibitors can be used to suppress breast cancer and ovarian cancer with mutations in BRCA-1/2 genes ("BRCAness" cancer) without com...Continue Reading

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