Preclinical evaluation of the PARP inhibitor BMN-673 for the treatment of ovarian clear cell cancer.

ABSTRACT:

Purpose

To determine if models of ovarian clear cell carcinomas (OCCCs) harbouring defects in homologous recombination (HR) DNA repair of double strand breaks (DSBs) are sensitive to cisplatin and/or PARP inhibition.

Experimental design

The HR status of 12 OCCC cell lines was determined using RAD51/γH2AX foci formation assays. Sensitivity to cisplatin and the PARP inhibitor BMN-673 was correlated with HR status. BRCA1, BRCA2, MRE11 and PTEN loss of expression was investigated as a potential determinant of BMN-673 sensitivity. A tissue microarray containing 50 consecutive primary OCCC was assessed for PTEN expression using immunohistochemistry.

Results

A subset of OCCC cells displayed reduced RAD51 foci formation in the presence of DNA DSBs, suggestive of HR defects. H

SUBMITTER: Wilkerson PM 

PROVIDER: S-EPMC5351612 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature