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Review
. 2025 Sep;32(9):1091-1101.
doi: 10.1111/iju.70100. Epub 2025 Jun 9.

PARP Inhibitors in Genitourinary Cancer: A New Paradigm Beyond Prostate Cancer

Yohei Okuda  1 , Taigo Kato  1 , Yu Ishizuya  1 , Takuji Hayashi  1 , Yoshiyuki Yamamoto  1 , Koji Hatano  1 , Atsunari Kawashima  1 , Junko Murai  2 , Norio Nonomura  1
Affiliations
Review

PARP Inhibitors in Genitourinary Cancer: A New Paradigm Beyond Prostate Cancer

Yohei Okuda et al. Int J Urol. 2025 Sep.

Abstract

Alterations in the homologous recombination repair genes, such as BRCA1 and BRCA2, are prevalent in various cancers, presenting a unique opportunity to develop synthetic lethal strategies that target homologous recombination deficiency (HRD). Poly ADP-ribose polymerase inhibitors (PARPis) have been developed to induce synthetic lethality in tumors with HRD by inhibiting the repair of single-strand DNA breaks. Beyond the initial approach to target cancers associated with HRD, the utility of PARPis has expanded to combination therapy with immune checkpoint inhibitors, anti-angiogenic drugs, or anti-androgen drugs based on the molecular biological rationale. In the field of genitourinary (GU) cancer, PARPis, such as olaparib, rucaparib, and talazoparib, are approved by the Food and Drug Administration in metastatic prostate cancer patients with BRCA1/2 mutations, sometimes in combination with other agents (e.g., olaparib plus abiraterone acetate, or talazoparib plus enzalutamide). More recently, pivotal clinical trials have broadened the potential of PARPis to the other GU cancers, including urothelial carcinoma and renal cell carcinoma. In this review, we examine the biomarkers for the response to PARPis beyond mutations in BRCA1/2 and discuss the current state and future perspectives of PARPis in GU cancers.

Keywords: PARP inhibitor; biomarkers; homologous recombination deficiency; synthetic lethality; urogenital cancer.

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Conflict of interest statement

Taigo Kato received lecture fees from Takeda Pharmaceutical Company Limited and Pfizer Global Supply Japan Inc. Junko Murai received lecture fees from Takeda Pharmaceutical Company Limited, Pfizer Global Supply Japan Inc., and AstraZeneca plc. The other authors declare that they have no conflicts of interest or financial ties related to this study. Norio Nonomura is an Editorial Board member of International Journal of Urology and a co‐author of this article. To minimize bias, he was excluded from all editorial decision‐making related to the acceptance of this article for publication.

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