Poly (ADP-ribose) polymerase (PARP) as target for the treatment of epithelial ovarian cancer: what to know

ABSTRACT

Introduction

Poly (ADP-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings of epithelial ovarian cancers (EOCs) with BRCA 1–2 gene mutation. PARP inhibitors are the first example of drugs targeting the loss of a gene suppressor: they block base-excision repair in the cancer cells, which have lost homologous recombination due to BRCA-mutation, resulting in loss of DNA repair and cell death, also known as synthetic lethality.

Areas covered

This article provides an overview of PARP inhibitors in OC treatment and also an extensive section on the combined strategies of PARP inhibitors, including approved as well as currently investigated drugs. It also offers a section on the use of predictive biomarkers for PARP inhibitors treatment. Ongoing trials, including novel combinations, are discussed.

Expert opinion

In recent years, there is increasing evidence that PARP inhibitor therapy can have life-long percussion in the treatment of EOC, even if some questions have to be solved yet, such as its use in combination therapy, the possibility to retreat with a PARP inhibitor, and finally how to overcome a resistance mechanism to this therapy. In this way, PARP inhibitors can obtain an important role in making a personalized therapeutic program in the case of first-line, neoadjuvant, platinum-sensitive, and resistant high-grade serous OC treatment.

KEYWORDS:

• Epithelial ovarian cancer
• PARP inhibitors
• olaparib
• niraparib
• rucaparib
• talazoparib
• veliparib

Article Highlights

• Olaparib, niraparib, and rucaparib have become fundamental in the therapeutic choices of patients affected by high-grade serous OC;

• Talazoparib and veliparib are emerging PARP inhibitors in earlier clinical development;

• Several studies have been conducted on the combination of PARP inhibitors with both platinum-based therapy and antiangiogenic drugs, showing that combined therapy allows increasing overall survival (OS) and progression-free survival (PFS);

• ‘FoundationFocusCDx BRCA LOH’ and ‘myChoice HRD’ (Myriad) are the two assay FDA approved as predictive biomarkers of sensitivity to PARP inhibitors.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.