Mutation profiles in circulating cell-free DNA predict acquired resistance to olaparib in high-grade serous ovarian carcinoma.

ABSTRACT: Although resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) has gradually become a major challenge in the maintenance therapy for high-grade serous ovarian carcinoma (HGSOC), there are no universal indicators for resistance monitoring in patients. A key resistance mechanism to PARPi is the restoration of homologous recombination repair (HRR), including BRCA reversion mutations and changes in DNA damage repair proteins. To explore mutation profiles associated with PARPi resistance, we undertook targeted 42-gene deep sequencing of circulating cell-free DNA (cfDNA) extracted from HGSOC patients pre- and post-treatment with olaparib maintenance therapy. We found that pathogenic germline mutations in the HRR pathway, including BRCA1/2, were strongly associated with improved clinical o

SUBMITTER: Hu D 

PROVIDER: S-EPMC9357630 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature