Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer

Abstract

Ovarian cancer is the most lethal gynecologic malignancy and the fifth most lethal cancer type overall in women. Ovarian cancer often presents genome instability, with almost half of the ovarian cancers harbor defects in one or more of the six DNA repair pathways, most of them in homologous recombination (HR). Targeting DNA repair genes has becoming a unique strategy to combat HR-deficient cancers in recent years. The multi-functional enzyme Poly ADP ribose polymerase (PARP) plays an impart role in DNA damage repair and genome stability. PARP inhibitors inhibit DNA repair pathways and cause apoptosis of cancer cells, especially in homologous recombination (HR)-deficient cells. PARP inhibitors (PARPi) have drawn increasing amount of attention due to their remarkable efficacy and low toxicity in treating HR-deficient ovarian cancers (i.e. BRCA1/2 mutated). To date, three PARP inhibitor drugs have been approved for treating ovarian cancer by FDA in United States, namely Olaparib, Rucaparib, and Niraparib. In this review, we summarized the current research progress of PARPi from basic science to clinical studies. We discussed the mechanism of action of PARP inhibitors and the exciting results from the clinical studies of the FDA-approved PARP inhibitors. We also highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics.

Keywords: Drug resistance; Mechanism; Ovarian cancer; PARP inhibitor; Progress.