A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation

ABSTRACT: Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2-related cancers. A test to identify additional HRR-deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient-derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay we scored archival breast tumor

SUBMITTER: Marta Castroviejo-Bermejo 

PROVIDER: S-SCDT-EMM-2018-09172 | biostudies-other |

REPOSITORIES: biostudies-other