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...

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Bibliographic Details
Published in:DNA repair Vol. 71; pp. 172 - 176
Main Author: D’Andrea, Alan D.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.11.2018
Subjects:
BRCA1/2
Homologous recombination
PARP1
Replication fork
BRCA1/2
Replication fork
PARP1
Homologous recombination
ISSN:1568-7864, 1568-7856, 1568-7856
Online Access:Get full text
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Summary: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.
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ISSN:1568-7864
1568-7856
1568-7856
DOI:10.1016/j.dnarep.2018.08.021