Ovarian Cancer Therapy: Homologous Recombination Deficiency as a Predictive Biomarker of Response to PARP Inhibitors

Abstract

Rowan E Miller,1,2 Osnat Elyashiv,1 Karim H El-Shakankery,1 Jonathan A Ledermann1,3 1Department of Medical Oncology, University College London Hospital, London, UK; 2Department of Medical Oncology, St Bartholomew’s Hospital, London, UK; 3UCL Cancer Institute, University College London, London, UKCorrespondence: Jonathan A Ledermann, UCL Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK, Email [email protected]: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionised the management of patients with high-grade serous and endometrioid ovarian cancer demonstrating significant improvements in progression-free survival. Whilst the greatest benefit is seen with BRCA1/2 mutant cancers, it is clear that the benefit extends beyond this group. This sensitivity is thought to be due to homologous recombination deficiency (HRD), which is present in up to 50% of the high-grade serous cancers. Several different HRD assays exist, which fall into one of three main categories: homologous recombination repair (HRR)-related gene analysis, genomic “scars” and/or mutational signatures, and real-time HRD functional assessment. We review the emerging data on HRD as a predictive biomarker for PARP inhibitors and discuss the merits and disadvantages of different HRD assays.Keywords: ovarian cancer, PARP inhibitors, BRCA mutations, homologous recombination deficiency, maintenance therapy

Keywords

• ovarian cancer
• parp inhibitors
• brca mutations
• homologous recombination deficiency
• maintenance therapy