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

5538Background: 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 poorly understood, not all patients with HRD cancers respond to these agents. Preclinical studies have demonstrated that changes in alternative DNA repair pathways affect PARP inhibitor (PARPi) sensitivity. As this has not previously been assessed in the clinical setting, we examined the relationship between HRD score, BRCA1 and BRCA2 mutation status, expression of NHEJ pathway repair proteins, and response of ovarian cancers treated with single agent PARPi. Methods: Archival biopsies from ovarian cancer patients undergoing treatment on a single-agent PARPi trial were stained for PARP1, RAD51, and multiple components of the nonhomologous end-joining (NHEJ) pathway, including 53BP1, KU70, KU80 and DNA-PKCS. Assays were validated by showing that the IHC signal was markedly attenuate...