Niraparib in breast cancer: evidence-based perspective on translational progress.

Abstract

Breast cancer is the most prevalent malignancy in women throughout the world, with a high level of heterogeneity concerning the subtypes, posing challenges to long-term treatment success. Among the emerging therapeutic strategies, poly (ADP-ribose) polymerase (PARP) inhibitors have shown promise in targeting tumors with defects in homologous recombination repair, particularly those harbouring BRCA1/2 mutations. Niraparib, a highly potent selective PARP1/2 inhibitor administered orally, has demonstrated a high anti-tumor response in ovarian cancer and is currently undergoing clinical trials in breast cancer treatment. Though niraparib possesses structural and functional similarities to other approved agents such as olaparib and talazoparib, it is not yet approved for breast cancer. This serves as a research gap that requires critical consideration of its therapeutic positioning. This review offers an in-depth examination of pharmacological profile, mechanism of action, resistance mechanism, and the benefits of niraparib in BRCA-mutated homologous recombination deficient breast cancer. We also summarise findings from major clinical trials that assess niraparib as monotherapy and in combination with chemotherapy, immune checkpoint inhibitors, and radiotherapy. Furthermore, this review critically evaluates the safety profile, pharmacokinetics, and ongoing clinical studies. Besides these, this article highlights the translational horizons and a new combination strategy that can possibly expand the use of niraparib to a wider patient group. By bridging mechanistic science and clinical applications, this review highlights the potential of niraparib to unlock synthetic lethality and shape the future landscape of precision oncology in breast cancer.