Zejula (niraparib)

Niraparib exhibits antitumor effects and promotes ferroptosis by inhibiting TM4SF1 expression through ALKBH1-mediated 6mA modification in BRCAwt OC. These findings emphasize the potential application of niraparib in BRCAwt OC and reveal the important role of epigenetic regulation in cancer treatment.

Calibration curves proved linear over the studied range, confirming the method's reliability. The results indicate that this stability-indicating approach is highly effective for routine in-process quality control, batch release testing, and long-term stability monitoring of niraparib drug substances.

One patient had a single brain metastasis and received comprehensive treatment including surgery, radiotherapy, chemotherapy, PD-1 inhibitor (tislelizumab), and PARP inhibitor (niraparib). The immune microenvironment characteristics of brain metastases (e.g., high PD-L1 expression, T-cell infiltration) may predict the efficacy of immunotherapy, but the prognosis for patients with multiple brain metastases remains poor. Further research is needed to explore the correlation between peripheral blood immune markers and treatment response in brain metastases.

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

Complete remission was obtained using stereotactic radiotherapy to the brain lesions, followed by platinum-based chemotherapy and maintenance therapy with bevacizumab and olaparib...Their role in this setting remains emerging and primarily supported by limited case reports and small series. Further studies are required to better define their role.

These data demonstrate clinical activity of niraparib in patients with metastatic or unresectable pancreatic cancers harboring DDR gene defects. Future studies are warranted to establish their roles in diverse genetic patient subpopulations.

P1/2, N=34, Active, not recruiting, Grupo Español de Tratamiento de Tumores de Cabeza y Cuello | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2027 --> Mar 2027

P2, N=63, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial primary completion date: Sep 2025 --> Jun 2026

P1/2, N=1000, Recruiting, Oslo University Hospital HF | N=6000 --> 1000

It details the efficacy of major PARPis (olaparib, niraparib, rucaparib, and fuzuloparib) in pivotal trials. Overcoming resistance requires a multipronged approach integrating deep molecular profiling, mechanism-informed combination therapies, and biomarker-driven clinical trial designs. Future progress hinges on translating biological insights into personalized treatment strategies to extend durable remission for a greater portion of patients, while also addressing the economic and ethical implications of long-term maintenance therapy.

Clinically, DNMT3B-high/ASS1-low tumors were associated with shorter progression-free survival, and serial plasma arginine declined prior to progression during niraparib maintenance, supporting plasma arginine dynamics as an exploratory candidate monitoring biomarker. Together, these findings define an epigenetically fixed arginine dependency in niraparib-resistant ovarian cancer and support partial dietary arginine restriction as a practical resensitization strategy.

HRR gene promoter methylation, particularly at specific BRCA1, BRCA2 and RAD51D CpG sites, robustly predicts PARPi sensitivity and independently stratifies PFS in HGSOC patients. The nomogram and PRS provide clinically actionable tools for individualized PARPi therapy.