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Niraparib in ovarian cancer: results to date and clinical potential

Journal

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
Volume 9, Issue 9, Pages 579-588

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/1758834017718775

Keywords

BRCA mutations; BRCAness; epithelial ovarian cancer; high-grade serous ovarian cancer; homologous recombination deficiency (HRD); niraparib; poly(ADP-ribose) polymerase inhibitors (PARPis); synthetic lethality concept; target therapy

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Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.

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