PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy in the western world, has been historically treated with surgery followed by chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most active new targeted therapies for the treatment of EOC. PARPis’ mechanism of action relies on their ability to interfere with DNA repair events leading ultimately to cell death, the biological concept known as synthetic lethality. Initially developed as maintenance therapy in patients with a response after platinum-based chemotherapy in a recurrent setting, PARPis are now approved as the frontline treatment strategy. The aim of this chapter is to examine PARPis’ antineoplastic activity and the clinical development studies that lead to their approval, as well as the safety and the management of adverse events associated with this new class of drugs. Lastly, the rational considerations for the use of PARPis in the frontline setting are discussed.