Parp inhibitor in oncology: a comprehensive analysis of mechanisms and therapeutic applications in ovarian cancer, non-ovarian gynecologic cancers, breast cancer and prostate cancer

Keywords

PARP inhibitor - treatment - cancer

Background: The poly-ADP ribose polymerase inhibitors (PARPi) are antineoplastic drugs highlighted in the treatment of neoplasms with mutations in the BRCA1/2 genes. The PARPi prevents double-strand break repair, which causes irreversible DNA damage, leading to cell death.

Objective: This study aimed to analyze the mechanisms and therapeutic applications of PARP inhibitors as a potential therapeutic option for the treatment of ovarian, no-ovarian gynecologic, breast and prostate cancers.

Methods: A literature review was done, including searches in the SciELO and PubMed databases using the keywords “PARP inhibitor”, “Treatment” and “Cancer” with the boolean operator “AND”. The selected articles include topics related to ovarian, non-ovarian gynecologic, breast or prostate cancers.

Results: PARP inhibitors demonstrate significant benefits in the treatment of gynecologic cancers, breast cancer, and ovarian cancer. In non-ovarian gynecological cancers, drugs like Niraparib and Dostarlimab improved progression-free survival (PFS) compared to chemotherapy, with a hazard ratio (HR) of 0.60 (95% CI, 0.43–0.82; p = 0.007). The combination of Durvalumab and Olaparib also showed favorable results, presenting a median PFS of 15.1 months, superior to the 9.6 months achieved by chemotherapy, with an HR of 0.55 (95% CI, 0.43–0.69; p<0.0001). In BRCA1/2 breast cancer, PARP inhibitors prolonged PFS, with an HR of 0.72 in patients previously treated with platinum and 0.68 in treatment-naive patients. In ovarian cancer, PARP inhibitors showed an HR of 0.46 in newly diagnosed patients and 0.36 in patients with BRCAm mutations. Although PARP inhibitors are generally well tolerated, there is an increase in hematological adverse events, including anemia (relative risk [RR] of 14.26), thrombocytopenia (RR of 6.86), and neutropenia (RR of 4.33).

Conclusion: PARP inhibitors emerge as a promising therapeutic approach in the treatment of gynecologic, breast and ovarian cancers. Data reveals that PARPi, such as Niraparib, Dostarlimab and Olaparib, provide improvements in PFS, especially in patients with mutations in the BRCA1 and BRCA2 genes. Although PARP inhibitors are generally well-tolerated, there is an increase in hematological adverse events. Thus, the continuity of research and the optimization of the use of these agents are essential to maximize their clinical benefits and minimize adverse effects.

Corresponding author: Larissa Maria Moraes Rodrigues de Souza (e-mail: [e-mail]).

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
06 May 2025