PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation
Poly (ADP-ribose) polymerase (PARP) 1 is an essential molecule in DNA damage response by sensing DNA damage and docking DNA repair proteins on the damaged DNA site through a type of posttranslational modification, poly (ADP-Ribosyl)ation (PARylation). PARP inhibitors, which inhibit PARylation throug...
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doaj-f93f2d7110b64bb0b70e98e2848d095c2020-11-25T03:32:57ZengMDPI AGCancers2072-66942020-02-0112239410.3390/cancers12020394cancers12020394PARP Inhibitors as Therapeutics: Beyond Modulation of PARylationAhrum Min0Seock-Ah Im1Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, KoreaCancer Research Institute, Seoul National University College of Medicine, Seoul 03080, KoreaPoly (ADP-ribose) polymerase (PARP) 1 is an essential molecule in DNA damage response by sensing DNA damage and docking DNA repair proteins on the damaged DNA site through a type of posttranslational modification, poly (ADP-Ribosyl)ation (PARylation). PARP inhibitors, which inhibit PARylation through competitively binding to NAD+ binding site of PARP1 and PARP2, have improved clinical benefits for BRCA mutated tumors, leading to their accelerated clinical application. However, the antitumor activities of PARP inhibitors in clinical development are different, due to PARP trapping activity beyond blocking PARylation reactions. In this review, we comprehensively address the current state of knowledge regarding the mechanisms of action of PARP inhibitors. We will also discuss the different effects of PARP inhibitors in combination with cytotoxic chemotherapeutic agents regarding the mechanism of regulating PARylation.https://www.mdpi.com/2072-6694/12/2/394parpparp inhibitorsparylationtrappingcancer therapeutic strategy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ahrum Min Seock-Ah Im |
spellingShingle |
Ahrum Min Seock-Ah Im PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation Cancers parp parp inhibitors parylation trapping cancer therapeutic strategy |
author_facet |
Ahrum Min Seock-Ah Im |
author_sort |
Ahrum Min |
title |
PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation |
title_short |
PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation |
title_full |
PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation |
title_fullStr |
PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation |
title_full_unstemmed |
PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation |
title_sort |
parp inhibitors as therapeutics: beyond modulation of parylation |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-02-01 |
description |
Poly (ADP-ribose) polymerase (PARP) 1 is an essential molecule in DNA damage response by sensing DNA damage and docking DNA repair proteins on the damaged DNA site through a type of posttranslational modification, poly (ADP-Ribosyl)ation (PARylation). PARP inhibitors, which inhibit PARylation through competitively binding to NAD+ binding site of PARP1 and PARP2, have improved clinical benefits for BRCA mutated tumors, leading to their accelerated clinical application. However, the antitumor activities of PARP inhibitors in clinical development are different, due to PARP trapping activity beyond blocking PARylation reactions. In this review, we comprehensively address the current state of knowledge regarding the mechanisms of action of PARP inhibitors. We will also discuss the different effects of PARP inhibitors in combination with cytotoxic chemotherapeutic agents regarding the mechanism of regulating PARylation. |
topic |
parp parp inhibitors parylation trapping cancer therapeutic strategy |
url |
https://www.mdpi.com/2072-6694/12/2/394 |
work_keys_str_mv |
AT ahrummin parpinhibitorsastherapeuticsbeyondmodulationofparylation AT seockahim parpinhibitorsastherapeuticsbeyondmodulationofparylation |
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1724565604251205632 |