Mechanisms of PARP inhibitor sensitivity and resistance

BRCA1 and BRCA2 deficient tumor cells are sensitive to inhibitors of Poly ADP Ribose Polymerase (PARP1) through the mechanism of synthetic lethality. Several PARP inhibitors, which are oral drugs and generally well tolerated, have now received FDA approval for various ovarian cancer and breast cance...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:DNA repair Jg. 71; S. 172 - 176
1. Verfasser: D’Andrea, Alan D.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 01.11.2018
Schlagworte:
BRCA1/2
Homologous recombination
PARP1
Replication fork
BRCA1/2
Replication fork
PARP1
Homologous recombination
ISSN:1568-7864, 1568-7856, 1568-7856
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:BRCA1 and BRCA2 deficient tumor cells are sensitive to inhibitors of Poly ADP Ribose Polymerase (PARP1) through the mechanism of synthetic lethality. Several PARP inhibitors, which are oral drugs and generally well tolerated, have now received FDA approval for various ovarian cancer and breast cancer indications. Despite their use in the clinic, PARP inhibitor resistance is common and develops through multiple mechanisms. Broadly speaking, BRCA1/2-deficient tumor cells can become resistant to PARP inhibitors by restoring homologous recombination (HR) repair and/or by stabilizing their replication forks. Here, we review the mechanism of PARP inhibitor resistance.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:1568-7864
1568-7856
1568-7856
DOI:10.1016/j.dnarep.2018.08.021