Reverse the resistance to PARP inhibitors

Yevgeniy Kim; Aleksei Kim; Ainur Sharip; Aigul Sharip; Juhong Jiang; Qing Yang; Yingqiu Xie

doi:10.7150/ijbs.17240

Reverse the resistance to PARP inhibitors

Yevgeniy Kim, Aleksei Kim, Ainur Sharip, Aigul Sharip, Juhong Jiang, Qing Yang, Yingqiu Xie

Department of Biology

Research output: Contribution to journal › Review article › peer-review

39 Citations (Scopus)

Abstract

One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs. This paper describes several molecular mechanisms of PARPi resistance which were reported most recently, and summarizes some strategies to reverse this type of drug resistance.

Original language	English
Pages (from-to)	198-208
Number of pages	11
Journal	International Journal of Biological Sciences
Volume	13
Issue number	2
DOIs	https://doi.org/10.7150/ijbs.17240
Publication status	Published - 2017

Keywords

DNA repair
Drug resistance
PARP
PARP inhibitor

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Applied Microbiology and Biotechnology
Molecular Biology
Developmental Biology
Cell Biology

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title = "Reverse the resistance to PARP inhibitors",

abstract = "One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs. This paper describes several molecular mechanisms of PARPi resistance which were reported most recently, and summarizes some strategies to reverse this type of drug resistance.",

keywords = "DNA repair, Drug resistance, PARP, PARP inhibitor",

author = "Yevgeniy Kim and Aleksei Kim and Ainur Sharip and Aigul Sharip and Juhong Jiang and Qing Yang and Yingqiu Xie",

note = "Funding Information: This work was supported by China-Kazakhstan collaboration grant (No. CK-07-09) to Yingqiu Xie and the National Natural Science Foundation of China (No. 81272901) to Juhong Jiang. The authors would like to thank the Department of Biology, SST, and Nazarbayev University for the support of acquired learning and research integrated teaching innovation of Biochemistry I course for undergraduate students. We would like to thank all the Biochemistry I course students who supported the assignment of the Biochemistry I course and the publication of their assignments.",

year = "2017",

doi = "10.7150/ijbs.17240",

language = "English",

volume = "13",

pages = "198--208",

journal = "International Journal of Biological Sciences",

issn = "1449-2288",

publisher = "Ivyspring International Publisher",

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T1 - Reverse the resistance to PARP inhibitors

AU - Kim, Yevgeniy

AU - Kim, Aleksei

AU - Sharip, Ainur

AU - Sharip, Aigul

AU - Jiang, Juhong

AU - Yang, Qing

AU - Xie, Yingqiu

N1 - Funding Information: This work was supported by China-Kazakhstan collaboration grant (No. CK-07-09) to Yingqiu Xie and the National Natural Science Foundation of China (No. 81272901) to Juhong Jiang. The authors would like to thank the Department of Biology, SST, and Nazarbayev University for the support of acquired learning and research integrated teaching innovation of Biochemistry I course for undergraduate students. We would like to thank all the Biochemistry I course students who supported the assignment of the Biochemistry I course and the publication of their assignments.

PY - 2017

Y1 - 2017

N2 - One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs. This paper describes several molecular mechanisms of PARPi resistance which were reported most recently, and summarizes some strategies to reverse this type of drug resistance.

AB - One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs. This paper describes several molecular mechanisms of PARPi resistance which were reported most recently, and summarizes some strategies to reverse this type of drug resistance.

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KW - Drug resistance

KW - PARP

KW - PARP inhibitor

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