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Niraparib is a poly-ADP ribose polymerase inhibitor used to treat recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer responding to platinum based chemotherapy.
Niraparib is a poly-ADP ribose polymerase inhibitor used to treat recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer responding to platinum based chemotherapy.
Niraparib is a potent and selective inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2. PARPs play an important role in DNA repair. They recognize and repair cellular DNA damage, such as single-strand breaks (SSBs) and double-strand breaks (DSBs). Different DNA repair pathways exist to repair these DNA damages, including the base excision repair (BER) pathway for SSBs and BRCA-dependent homologous recombination for DSBs. If BER is impaired, SSBs accumulate and become DSBs, forcing cells to rely on other repair pathways, mainly the homologous recombination (HR) and the nonhomologous end joining, to repair DNA damages. However, some cells can have defective or deficient HR resulting from specific mutations in DNA repair genes, such as BRCA1 and 2. Inhibiting PARPs in the presence of HR deficiency leads to a phenomenon called 'synthetic lethality,' whereby the PARP inhibitor impedes BER, leading to genetic instability and cell death. Selectivity towards PARP-1 and PARP-2 is 100-fold higher than for other PARP family members. Niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death.
Niraparib is indicated for the maintenance treatment of adult patients with advanced or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. In Canada and the US, niraparib is also available in a combination product with abiraterone, which is indicated with prednisone for the treatment of adults with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). In Canada, this combination product is also used with prednisolone and is reserved for patients who are asymptomatic or mildly symptomatic, and in whom chemotherapy is not clinically indicated.
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