TY - JOUR

T1 - DNA Repair Enzymes as Promising Targets in Oncotherapy

AU - Zakharenko, A. L.

AU - Lebedeva, N. A.

AU - Lavrik, O. I.

N1 - Publisher Copyright: © 2018, Pleiades Publishing, Ltd.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - DNA repair is a complicated process that occurs due to a network of different pathways and mechanisms for correction of DNA damages during the normal DNA biosynthesis and under the influence of external and internal factors. The study of these mechanisms and their regulation is closely related to both diagnostics and the search for ways of treating various diseases, including oncological ones. Malignant neoplasms are one of the three most widespread diseases in the world, which unfortunately often become the reason for a lethal outcome. Traditional cancer therapy aims to the DNA damage in malignant cells, and its result depends on the efficiency of the repair systems. In many cancer cells, the individual DNA repair enzymes are overexpressed, which promotes the resistance of these tumors to the therapy. On the other hand, defects in the DNA repair systems in cancer cells allow researchers to find both appropriate biomarkers for diagnostics and targets for the development of the specific and effective therapy. Currently, DNA repair inhibitors are being actively developed in order to increase the sensitivity of the tumor cells to traditional chemotherapy. The principle of synthetic lethality is used to create cell-specific drugs and to improve the effectiveness of the treatment. In this review, we discuss the current state of research and prospects for the development of inhibitors for five important DNA repair enzymes.

AB - DNA repair is a complicated process that occurs due to a network of different pathways and mechanisms for correction of DNA damages during the normal DNA biosynthesis and under the influence of external and internal factors. The study of these mechanisms and their regulation is closely related to both diagnostics and the search for ways of treating various diseases, including oncological ones. Malignant neoplasms are one of the three most widespread diseases in the world, which unfortunately often become the reason for a lethal outcome. Traditional cancer therapy aims to the DNA damage in malignant cells, and its result depends on the efficiency of the repair systems. In many cancer cells, the individual DNA repair enzymes are overexpressed, which promotes the resistance of these tumors to the therapy. On the other hand, defects in the DNA repair systems in cancer cells allow researchers to find both appropriate biomarkers for diagnostics and targets for the development of the specific and effective therapy. Currently, DNA repair inhibitors are being actively developed in order to increase the sensitivity of the tumor cells to traditional chemotherapy. The principle of synthetic lethality is used to create cell-specific drugs and to improve the effectiveness of the treatment. In this review, we discuss the current state of research and prospects for the development of inhibitors for five important DNA repair enzymes.

KW - apurinic/apyrimidinic endonuclease 1

KW - DNA polymerase β

KW - Inhibitors of DNA repair enzymes

KW - poly (ADP-ribose) polymerase

KW - tyrosyl-DNA phosphodiesterase 1

KW - POLY(ADP-RIBOSE) POLYMERASE

KW - SOMATOSTATIN ANALOGS

KW - STRAND BREAK REPAIR

KW - CANCER-CELL-GROWTH

KW - DNA polymerase ss

KW - REVERSE-TRANSCRIPTASE

KW - PHOSPHODIESTERASE 1 TDP1

KW - TOPOISOMERASE-I

KW - SMALL-MOLECULE INHIBITOR

KW - BASE EXCISION-REPAIR

KW - BIOLOGICAL EVALUATION

UR - http://www.scopus.com/inward/record.url?scp=85043988174&partnerID=8YFLogxK

U2 - 10.1134/S1068162017060140

DO - 10.1134/S1068162017060140

M3 - Review article

AN - SCOPUS:85043988174

VL - 44

SP - 1

EP - 18

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 1

ER -