PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation.
PARP
PARP inhibitors
PARylation
cancer therapeutic strategy
trapping
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
08 Feb 2020
08 Feb 2020
Historique:
received:
30
12
2019
revised:
01
02
2020
accepted:
05
02
2020
entrez:
13
2
2020
pubmed:
13
2
2020
medline:
13
2
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32046300
pii: cancers12020394
doi: 10.3390/cancers12020394
pmc: PMC7072193
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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