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Review
. 2014 Jan;25(1):32-40.
doi: 10.1093/annonc/mdt384. Epub 2013 Nov 12.

PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies

J-M Lee  1 , J A Ledermann, E C Kohn
Affiliations
Review

PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies

J-M Lee et al. Ann Oncol. 2014 Jan.

Abstract

Poly(ADP-ribose)polymerase inhibitors (PARPis) have shown promising activity in patients with BRCA1/2 mutation-associated (BRCA1/2(MUT+)) ovarian and breast cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of sporadic high-grade serous ovarian cancer, and cancers defective in DNA repair pathways, such as prostate, endometrial, and pancreatic cancers. Several PARPis are currently in phase 1/2 clinical investigation, with registration trials now being designed. Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers. Understanding more about the molecular abnormalities involved in BRCA-like tumors, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers, is critical to rapidly advancing the field of PARPi therapy and improve clinical outcomes.

Keywords: brca-like cancers; brca1/2 mutation; brca1/2 mutation-associated cancers; parp inhibitor.

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Figures

Figure 1.
Figure 1.
Double-strand break repair and single-strand break repair with poly(ADP-ribose)polymerase inhibitors (PARPis).
Figure 2.
Figure 2.
γH2AX binds to DNA DSBs and RAD51 initiates repair protein assembly in the homologous recombination (HR) pathway.
See this image and copyright information in PMC

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