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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Four PARP inhibitors reached the approval stage by the FDA and EMA between 2016 and 2019 (Figure 5.104). These are olaparib (LynparzaTM), developed by AstraZeneca and licensed for ovarian, fallopian tube, and peritoneal cancers (starting treatment no later than eight weeks after completion of a final dose of a platinum-containing regimen); talazoparib (AlzennaTM), developed by Pfizer and used for breast cancer; rucaparib (RubracaTM), developed by Clovis Oncology and used for ovarian, fallopian tube, and peritoneal cancers; and niraparib (ZejulaTM), developed by Tesaro and used for fallopian tube and peritoneal cancer. All of these agents are orally available and recommended for patients with mutated BRCA for which a pharmacogenomic test is available (see Chapter 11). A molecular model of olaparib binding to the NAD+-binding site of the PARP1 is shown in Figure 5.105. Structures of the approved PARP inhibitors olaparib (LynparzaTM), talazoparib (AlzennaTM), rucaparib (RubracaTM), and niraparib (ZejulaTM).Molecular model of the PARP inhibitor olaparib (dark grey) occupying the NAD+-binding site of the DNA-repair protein PARP-1 (From the PDB Database: Entry 5DS3).
Budget impact analysis of niraparib and olaparib for maintenance treatment of platinum-sensitive, recurrent ovarian cancer in the US
Published in Journal of Medical Economics, 2019
Oral poly ADP-ribose polymerase (PARP) inhibitor is a new class of targeted therapy for ovarian cancer. PARP inhibitors can target cancer cells with homologous DNA repair defects through a mechanism called “synthetic lethality”8. Niraparib (Zejula) and olaparib (Lynparza) are two PARP inhibitors recently approved by FDA in 2017 as maintenance therapy for platinum-sensitive, recurrent ovarian cancer patients after first-line chemotherapy9,10. The approvals were based on clinical trials of NOVA (NCT01847274), Study 19 (NCT00753545), and SOLO-2 (NCT01874353), and both drugs significantly increased the progression-free survival (PFS) duration in patients in the pivotal trials8,11,12. However, these drugs are also associated with high drug prices. Some studies have suggested that PARP inhibitors may not be cost-effective in treating ovarian cancer, despite the clinical efficacy13,14.
Poly (ADP-ribose) polymerase (PARP) as target for the treatment of epithelial ovarian cancer: what to know
Published in Expert Opinion on Investigational Drugs, 2021
Luigi Della Corte, Virginia Foreste, Claudia, Di Filippo, Pierluigi Giampaolino, Giuseppe Bifulco
‘myChoice HRD’ (Myriad) is a laboratory test that detects HRD status. A positive HRD status means that there are mutations in BRAC1 and BRCA2 genes or a high Genomic Instability Score (GIS) in patients with OC. It is performed on genomic DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue. With a positive HRD status, a patient’s DNA is unable to repair. When patients with OC test positive for HRD, the doctor can determine if they are eligible for treatment with Zejula® (niraparib) [88].