Proteasome inhibition induces a BRCAness-like state and sensitises HR-proficient ovarian cancer models to PARP inhibitors

Background Poly (ADP-ribose) polymerase inhibitors (PARPi) have improved outcomes in ovarian cancer with homologous recombination deficiency (HRD). However, approximately half of high-grade serous ovarian cancers retain intact homologous recombination repair and are classified as homologous recombination–proficient (HRP), limiting the clinical benefit of PARPi in this population. Strategies capable of pharmacologically inducing a functional HRD-like state may expand the therapeutic scope of PARP