Expanding the utility of PARP inhibitors in prostate cancer using combination therapy with androgen receptor pathway inhibitors

Prostate cancer is one of the most diagnosed cancers in males, and advanced disease remains difficult to treat. This thesis investigates how to improve treatment by combining PARP inhibitors with androgen receptor inhibitors. Using patient-derived models, it shows that PARP inhibitor alone benefits only a small subset of tumours, whereas combination therapy can suppress the growth of a broader range of prostate cancers, including tumours without DNA repair defects, by increasing DNA damage and reducing tumour cell proliferation. These findings may help extend PARP inhibitor benefit to more prostate cancer patients and guide future clinical studies of the combination therapy.