Ovarian cancer is the second most common gynecologic malignancy in the United States (US) and the most common cause of gynecologic cancer-related death. The majority of ovarian cancers ultimately recur despite excellent response rates to upfront platinum and taxane-based chemotherapy. Maintenance therapy after frontline treatment has emerged in recent years as an effective tool for extending the platinum-free interval of these patients. Maintenance therapy with poly (ADP-ribose) polymerase inhibitors (PARPi) in particular has become part of standard of care in the upfront setting and in patients with platinum-sensitive disease. HR deficient (HRD) tumors have a nonfunctioning homologous recombination repair (HRR) pathway and respond well to PARPi, which takes advantage of synthetic lethality by concomitantly impairing DNA repair mechanisms. Conversely, patients with a functioning HRR pathway, i.e. HR proficient (HRP) tumors, can still elicit benefit from PARPi, but the efficacy is not as remarkable as what is seen in HRD tumors. PARPi are ineffective in some patients due to HR proficiency, which is either inherent to the tumor or potentially acquired as a method of therapeutic resistance. This review seeks to outline current strategies employed by clinicians and scientists to overcome PARPi resistanceeither acquired or inherent to the tumor.
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