Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction

Ying-Cheng Chiang; Po-Han Lin; Wen-Fang Cheng

doi:10.3389/fonc.2021.675972

Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction

Front Oncol. 2021 Oct 14:11:675972. doi: 10.3389/fonc.2021.675972. eCollection 2021.

Authors

Ying-Cheng Chiang¹, Po-Han Lin^{2

3}, Wen-Fang Cheng^{1

4

5}

Affiliations

¹ Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
³ Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁴ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of BRCA mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development.

Keywords: PARP inhibitor; RAD51 foci formation; epithelial ovarian cancer; genomic scar; homologous recombination deficiency; mutational signatures.

Publication types

Review