niraparib

Overview

Niraparib is an orally bioavailable poly(ADP-ribose) polymerase inhibitor used in oncology, particularly in the context of ovarian cancer maintenance therapy after platinum-based chemotherapy. It targets PARP enzymes, especially parp1 and PARP2, thereby interfering with DNA repair and promoting selective cytotoxicity in tumor cells with impaired DNA damage response pathways. This mechanism is especially relevant in cancers associated with homologous recombination defects, including tumors with BRCA1 and BRCA2 alterations.

As a therapeutic agent, niraparib is part of the broader class of poly(adenosine diphosphate ribose) polymerase inhibitors and is studied both for its antitumor activity and for the mechanisms that limit its effectiveness. Recent research has also examined its pharmacologic properties, formulation quality, and adverse-effect profile, reflecting its established role in clinical oncology and ongoing efforts to optimize its use.

Focus of Latest Publications

Recent publications have focused on niraparib from several complementary angles: clinical use, resistance mechanisms, toxicity prediction, and analytical characterization.

In ovarian cancer, niraparib continues to be described as an effective maintenance therapy after platinum-based chemotherapy. One multicenter study in Japanese patients specifically investigated risk factors for niraparib-induced severe anemia, reinforcing the importance of hematologic monitoring during treatment. Another analysis from the phase II NEWTON trial (ENGOT-ov49) examined rational dose adjustment to reduce adverse reactions in patients with platinum-sensitive recurrent ovarian cancer. In that context, retrospective analyses of niraparib trials showed that baseline platelets and body weight were associated with the occurrence of grade 3 or higher thrombocytopenia, supporting individualized dosing strategies.

Niraparib has also been explored beyond ovarian cancer. A phase II trial evaluated niraparib in patients with advanced pancreatic cancer harboring pathogenic variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2. This reflects ongoing interest in using PARP inhibition in tumors with DNA repair defects, where synthetic lethality may be therapeutically relevant.

Mechanistically, recent research has also addressed resistance to PARP inhibitors. A study on tumor cell-derived interferon signaling and osteopontin-enriched macrophage niches used specimens from a prospective neoadjuvant niraparib monotherapy trial in treatment-naive, high-grade serous ovarian cancer. The investigators integrated spatial profiling, single-cell RNA sequencing, and multiplex immunohistochemistry to identify two therapeutic-modulated cellular neighborhoods: an IFN-positive tumor cell-enriched niche that expanded in resistant lesions, and a tumor-associated macrophage niche that persisted but acquired enhanced immunosuppressive features. This work links niraparib response and resistance to changes in the tumor microenvironment, including regulatory T cell and T-lymphocyte-associated immune context.

A separate resistance-focused publication on PARP inhibitor resistance mechanisms in ovarian cancer noted that P-gp/ABCB1 influences resistance to paclitaxel and olaparib, while similar niraparib resistance mechanisms had not been described. This highlights an important distinction in the resistance landscape between niraparib and other PARP inhibitor or taxane-based therapies, including olaparib, carboplatin, doxorubicin, and taxane regimens used in ovarian cancer.

Finally, niraparib has also been the subject of pharmaceutical and analytical research. One study developed a robust isocratic HPLC-UV method for comprehensive determination of the enantiomeric impurity (R-isomer) in niraparib drug substance. This work is relevant to drug quality control and stereochemical purity, which are important for manufacturing and regulatory assessment.

Key Publications

Jul Identification of novel drug-specific PARP inhibitor resistance mechanisms in ovarian cancer-implications for clinical practice. (British journal of cancer, 2026, PMID 41998207): "We have shown that P-gp/ABCB1 influences resistance to paclitaxel and olaparib, but similar niraparib resistance mechanisms have not been described [2, 3]."
Jul A Novel, Robust, and Isocratic HPLC-UV Method for the Comprehensive Determination of Enantiomeric Impurity (R-Isomer) in Niraparib Drug Substance. (Chirality, 2026, PMID 42304726): "Niraparib is a potent, orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, specifically targeting PARP-1 and PARP-2 to induce selective cytotoxicity in malignancies by disrupting DNA repair mechanisms."
May Rational adjustment of dose to reduce adverse reactions (RADAR) in patients with platinum-sensitive recurrent ovarian cancer: Results from the phase II NEWTON trial (ENGOT-ov49). (European journal of cancer (Oxford, England : 1990), 2026, PMID 41950571): "Retrospective analyses of niraparib trials showed that baseline platelets and weight were associated with occurrence of G ≥3 thrombocytopenia."
May A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2. (Clinical cancer research : an official journal of the American Association for Cancer Research, 2026, PMID 41686836): "A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2."
May Risk Factors for Niraparib-induced Severe Anemia in Japanese Patients With Ovarian Cancer: A Multicenter Study. (Anticancer research, 2026, PMID 42049354): "Niraparib is an effective maintenance therapy after platinum-based chemotherapy for ovarian cancer."
Apr Tumor cell-derived IFN spatially reprograms osteopontin-enriched macrophage niches to promote PARP inhibitor resistance. (The Journal of clinical investigation, 2026, PMID 41734034): "Leveraging specimens from a prospective neoadjuvant niraparib monotherapy trial in treatment-naive, high-grade serous ovarian cancer, we integrated PhenoCycler-Fusion spatial profiling, scRNA-Seq, and multiplex immunohistochemistry to identify 2 therapeutic-modulated cellular neighborhoods: an IFN+ tumor cell-enriched niche that expands in resistant lesions and a niche enriched in tumor-associated macrophage (TAM) that persists but acquires enhanced immunosuppressive features."
Apr Exploration of a Novel Thiadiazole Derivative: Design, Synthesis, Biological Evaluation (In Vitro and in Silico), and DFT Studies. (Journal of fluorescence, 2026, PMID 41673348): "The biological potential of compound 5 was then explored through in vitro cytotoxicity screening against three distinct human cancer cell lines: MCF-7 (breast carcinoma), A549 (lung carcinoma), and PC3 (prostate carcinoma)."