Androgen receptor inhibition extends PARP inhibitor activity in prostate cancer models beyond BRCA mutations and defects in homologous recombination repair.

ABSTRACT: Clinical trials show benefit of the combination of poly(ADP-ribose) polymerase inhibitors (PARPi) with androgen receptor (AR) pathway inhibitors (ARPi) in metastatic, castration-resistant prostate cancer. While benefit was evident in patients with tumours harbouring mutations in homologous recombination repair (HRR) genes, improved outcomes were also observed in the absence of such alterations. Although there is literature linking AR with DNA repair, the basis of the interaction between the AR and PARP is unclear. We show that benefit of the combination of ARPi and PARPi in prostate cancer models with no HRR mutations requires ARPi-responsive cells and a PARPi with PARP1-trapping activity, and does not involve an effect of PARPi treatment in modulating AR transcription. Combination benefit

SUBMITTER: Illuzzi G 

PROVIDER: S-EPMC12501778 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature