53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer.

ABSTRACT:

Objective

Poly(ADP-ribose) polymerase (PARP) inhibitors have shown substantial activity in homologous recombination- (HR-) deficient ovarian cancer and are undergoing testing in other HR-deficient tumors. For reasons that are incompletely understood, not all patients with HR-deficient cancers respond to these agents. Preclinical studies have demonstrated that changes in alternative DNA repair pathways affect PARP inhibitor (PARPi) sensitivity in ovarian cancer models. This has not previously been assessed in the clinical setting.

Methods

Clonogenic and plasmid-based HR repair assays were performed to compare BRCA1-mutant COV362 ovarian cancer cells with or without 53BP1 gene deletion. Archival biopsies from ovarian cancer patients in the phase I, open-label clinical trial of

SUBMITTER: Hurley RM 

PROVIDER: S-EPMC6430710 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature