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Overview of PARP and DNA damage1-3

ZEJULA (niraparib) is a poly(ADP-ribose) polymerase (PARP1/2) inhibitor. Multiple factors can cause different types of DNA damage, including single-strand and double-strand breaks. DNA damage and the resulting genetic aberrations can lead to the development of many cancers, such as ovarian cancer. Thus, our cells have evolved an intricate series of DNA repair mechanisms to preserve genomic stability.

Repair of single-strand breaks and the role of PARP4-7

Single-strand breaks in DNA are restored by several mechanisms, including the base excision repair pathway. The PARP family of enzymes plays an important role in detecting and repairing these sites of damage. PARP binds to DNA breaks and generates poly(ADP-ribose) chains, which act as beacons to recruit other repair proteins.

Double-strand breaks and the homologous recombination (HR) pathway2,3,4,8–10

If a single-strand break remains unresolved, it may result in a double-strand break. The homologous recombination pathway is a major mechanism responsible for repairing such breaks. This process is mediated, in part, by tumour suppressors BRCA1 and BRCA2 and by the MRN-complex proteins. When the base excision repair pathway is compromised, HR can compensate to maintain genomic integrity. However, many cancer cells have intrinsic defects in HR, leading to accumulation of double-strand breaks, genomic instability, and potential malignant transformation.

ZEJULA’s (niraparib) mechanism of action1,6,8,9,11–15

ZEJULA (niraparib) inhibits the catalytic activity of PARP and traps PARP at sites of DNA damage. This impairs the recruitment of repair proteins and prevents the repair of single-strand breaks, causing an accumulation of double-strand breaks. In HRd cancer cells, blocking both the base excision and HR pathways leads to genomic instability and cancer cell death – a concept known as synthetic lethality.

Mechanism of action graphic Mechanism of action graphic

Figure adapted from Konecny G, et al. 2016.16

ZEJULA (niraparib) is the only 1L maintenance monotherapy proven in two phase III clinical trials in advanced ovarian cancer 17–19

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ZEJULA is indicated:20

  • as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.
  • as monotherapy for the maintenance treatment of adult patients with platinum-based relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

References

  1. Ison G, et al. Clin Cancer Res. 2018;24(17):4,066–4071. Available here.
  2. Polo SE, Jackson SP. Genes Dev. 2011;25(5):409–433. Available here.
  3. Lord CJ, Ashworth A. Nature. 2012;481 (7,381):287–294. Available here.
  4. Gee ME, et al. J Ovarian Res. 2018;11(1):50. Available here.
  5. Gupte R, et al. Genes Dev. 2017;31(2):101–126. Available here.
  6. Javle M, Curtin NJ. Br J Cancer. 2011;105(8):1,114–1122. Available here.
  7. Eustermann S, et al. Mol Cell. 2015;60(5):742–754. Available here.
  8. De Lorenzo SB, et al. Front Oncol. 2013;3:228. Available here.
  9. Sonnenblick A, et al. Nat Rev Clin Oncol. 2015;12(1):27–41. Available here.
  10. O’Connor MJ. Mol Cell. 2015;60(4):547–560. Available here.
  11. Jiang X, et al. Cancer Manag Res. 2019;11 :4,371–43,90. Available here.
  12. Dziadkowiec KN, et al. Menopause Rev. 2016;15(4):215–219. Available here.
  13. Min A, Im S-A. Cancers. 2020;12(2):394. Available here.
  14. Murai J, et al. Cancer Res. 2012;72(21 ):5,588–5,599. Available here.
  15. Jones P, et al. J Med Chem. 2009;52(22):7,170–7,185. Available here.
  16. Koneczny G, Kristeleit R. Br J Cancer. 2016;115(10):1,157–1,173. Available here.
  17. González Martín A, et al. N Engl J Med. 2019;381(25):2391–2402. Available here.
  18. Monk B, et al. Ann Oncol. 2024;35(11):981–992. Available here.
  19. Li N, et al. JAMA Oncol. 2023;9(9):1230–1237. Available here.
  20. ZEJULA (niraparib) Summary of Product Characteristics. September 2025. ​

Abbreviations

1L, first-line; DNA, deoxyribonucleic acid; FIGO, Federation of Gynaecology and Obstetrics; HRd, homologous recombination deficient; MoA, mechanism of action; PARPi, poly(ADP-ribose) polymerase inhibitor.

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk or search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GlaxoSmithKline on 0800 221 4411 or UKSafety@gsk.com

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June 2026 | PM-GB-NRP-WCNT-240007