PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer.

Automated summary

Ovarian cancer, characterized by high death-to-incidence ratio, is effectively treated with platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) that show benefits even in the absence of BRCA mutation. However, resistance to PARP inhibitors is a challenge, prompting research for new treatment strategies. This critical review provides an overview of the current landscape and future perspectives for enhancing the effectiveness of PARP inhibitors in newly diagnosed and recurrent ovarian cancer.