Therapeutic applications of PARP inhibitors in ovarian cancer

Abstract

Ovarian cancer is the most lethal gynecologic malignancy with a high recurrence rate. Poly(ADP-ribose) polymerase inhibitors (PARPi) are one of the most active new therapies for treatment of ovarian cancer. These treatment modalities are based on the mechanisms of "synthetic lethal" and "PARP trapping", especially for patients with homologous recombination deficiencies, and they demonstrate a high survival advantage. However, resistance to PARPi is an emerging problem. Identifying potential biomarkers to monitor the resistance and developing drug combination strategies are effective ways to address PARPi resistance. This review introduces the mechanisms of anticancer activity of PARPi and the developmental history in clinical research. Moreover, this paper systematically analyzes the functions of PARP family proteins. Additionally, this work highlights the treatment prospects of the combination of immunotherapy and PARPi in ovarian cancer. Finally, we propose several novel technologies to overcome the limitations of current preclinical studies and utilize them to select potential targets for combined drug therapy and identify biomarkers of PARPi resistance in ovarian cancer.

Keywords: Combination therapy; Ovarian cancer; PARP inhibitor; Resistance; Synthetic lethal.