Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.

ABSTRACT: Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity associating with homologous recombination DNA repair defects. We now report targeted and whole-exome sequencing of serial circulating cell-free DNA (cfDNA) samples collected during this trial. Decreases in cfDNA concentration independently associated with outcome in multivariable analyses (HR for overall survival at week 8: 0.19; 95% CI, 0.06-0.56; P = 0.003). All tumor tissue somatic DNA repair mutations were detectable in cfDNA; allele frequency of somatic mutations decreased selectively in responding patients (χ²P < 0.001). At disease progress

SUBMITTER: Goodall J 

PROVIDER: S-EPMC6143169 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature