Homologous recombination deficiency (HRD) is a key biomarker associated with increased sensitivity to PARP inhibitors (PARPi) in advanced epithelial ovarian cancer. Accurate identification of HRD status is essential for selecting patients most likely to benefit from these therapies. Current diagnostic approaches combine sequencing to detect mutations in homologous recombination repair genes—particularly BRCA1 and BRCA2—with genome-wide analysis of structural genomic alterations indicative of HRD. This review briefly outlines the biological basis of HRD and its clinical significance and then focuses on currently available assays for HRD assessment. We compare their molecular strategies, including the use of targeted gene panels and genomic instability metrics such as loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. The review also highlights the strengths and limitations of each platform and discusses their role in guiding clinical decision-making. Challenges related to dynamic tumor evolution and the interpretation of HRD status in recurrent disease settings are also addressed.

Ovarian cancer recurs in approximately 70% of cases. In platinum-sensitive relapse, platinum-based therapy remains the backbone of treatment, with optional integration of secondary cytoreductive surgery achieving complete resection and/or hyperthermic intraperitoneal chemotherapy, although evidence remains conflicting. Bevacizumab combined with chemotherapy improves progression-free survival (PFS) but not overall survival (OS). Poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance significantly prolongs PFS in patients with germline or somatic BRCA mutations; its use is currently restricted to this subgroup. Immune checkpoint inhibitors have failed to demonstrate benefit in phase III trials. In platinum-resistant ovarian cancer (PROC), platinum rechallenge retains activity in selected patients. Bevacizumab with chemotherapy improves PFS without OS benefit. Novel antibody-drug conjugates (ADCs) are emerging as promising options: mirvetuximab soravtansine significantly improved PFS (5.6 vs 4.0 months) and OS (16.5 vs 12.8 months) compared with chemotherapy in folate receptor alpha-high PROC (MIRASOL). Trastuzumab deruxtecan has shown high response rates in HER2-expressing disease. Other ADCs and targeted agents, including the WEE1 inhibitor adavosertib, are currently under evaluation. Biomarker-driven therapies are reshaping the management of recurrent ovarian cancer. Future strategies should prioritise improved patient selection and earlier integration of targeted therapies.