[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-367819-105":59,"doc-detail-367819-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","parp-inhibitors-in-genitourinary-cancer-a-new-paradigm-beyond-prostate-cancer","PARP Inhibitors in Genitourinary Cancer: A New Paradigm Beyond Prostate Cancer","","Homologous recombination repair gene alterations, including BRCA1 and BRCA2, enable synthetic lethal strategies targeting homologous recombination deficiency (HRD). Poly ADP-ribose polymerase inhibitors (PARPis) induce tumor cell death by suppressing repair of single-strand DNA breaks, and their clinical role has expanded beyond HRD-linked monotherapy. In genitourinary cancers, PARPis such as olaparib, rucaparib, and talazoparib are established in metastatic prostate cancer and are now under evaluation in urothelial carcinoma and renal cell carcinoma. This review summarizes PARPi response biomarkers beyond BRCA1/2 and outlines current and future directions.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/parp-inhibitors-in-genitourinary-cancer-a-new-paradigm-beyond-prostate-cancer/367819/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/parp-inhibitors-in-genitourinary-cancer-a-new-paradigm-beyond-prostate-cancer/367819.png","ImageObject",300,407,{"name":92,"@type":93},"4398046744996","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How do PARP inhibitors induce synthetic lethality in HRD tumors?","Question",{"text":112,"@type":113},"PARPis inhibit the repair of single-strand DNA breaks, leading to replication-associated double-strand breaks and cancer cell death. HRD tumors are especially vulnerable because homologous recombination-mediated DSB repair is impaired.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which PARP inhibitors are approved for BRCA1/2-mutant metastatic prostate cancer?",{"text":117,"@type":113},"Olaparib, rucaparib, and talazoparib are approved for metastatic prostate cancer patients with BRCA1/2 mutations, with some regimens also used in combination with other agents.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the review’s focus regarding biomarkers beyond BRCA1/2?",{"text":121,"@type":113},"The review examines biomarkers that predict PARPi response in genitourinary cancers beyond BRCA1/2 mutations. It also discusses the current state and future perspectives of PARPis across GU cancer types.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},367819,1790216875,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":66,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},4398046744996,"International Journal of Urology  \nPARP Inhibitors in Genitourinary Cancer: A New Paradigm Beyond Prostate Cancer  \nYohei Okuda1  | Taigo Kato1  | Yu Ishizuya1  | Takuji Hayashi1 | Yoshiyuki Yamamoto1  | Koji Hatano1 | Atsunari Kawashima1  | Junko Murai2 | Norio Nonomura1  \n1Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan | 2Department of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Toon, Japan  \nCorrespondence: Taigo Kato ([kato@uro.med.oaska-u.ac.jp](kato@uro.med.oaska-u.ac.jp))  \nReceived: 19 November 2024 | Revised: 22 April 2025 | Accepted: 30 April 2025  \nKeywords: biomarkers | homologous recombination deficiency | PARP inhibitor | synthetic lethality | urogenital cancer  \nABSTRACT  \nAlterations 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.  \n1 | Introduction  \nPoly(ADP-ribose) polymerases (PARPs) are enzymes involved in poly ADP-ribosylation (PARylation), a post-translational modification critical for repairing DNA single-strand breaks (SSBs) . Among the 17 PARP family members, PARP1 and PARP2 are the primary mediators of DNA repair and genomic stability, especially in response to SSBs [1–3] . Inhibition of these enzymes leads to SSB accumulation and replication-associated  \ndouble-strand breaks (DSBs), ultimately triggering cancer cell death—a concept that led to the development of PARP inhibitors (PARPis) [4–6] .  \nThe clinical relevance of PARPis grew dramatically following the discovery of synthetic lethality in BRCA1/2-mutated tumors, which lack homologous recombination (HR)-mediated DSB repair [7, 8] . BRCA1 and BRCA2 genes are central to the HR repair (HRR) pathway, and their inactivation results in  \n\n| Abbreviations: ACC, adrenocortical carcinoma; BER, base excision repair; BSC, best supportive care; CAR-T cell, chimeric antigen receptor T-cell; CI, confidence interval; DCR, disease control rate; DDR, dna damage repair; DSBs, double-strand breaks; FAP, familial adenomatous polyposis; GCT, germ cell tumor; GU, genitourinary; HR, homologous recombination; HRD, homologous recombination deficiency; HRR, homologous recombination repair; ICI, immune checkpoint inhibitor; KIRC, kidney renal clear cell carcinoma; KPRC, kidney papillary renal cell carcinoma; LOH, loss of heterozygosity; MIBC, muscle-invasive bladder cancer; NHEJ, non-homologous end joining; ORR, objective response rate; OS, overall survival; PARP, poly ADP-ribose polymerase; PARPi, PARP inhibitor; PBC, platinumbased chemotherapy; PC, prostate cancer; PCC, pheochromocytoma; PFS, progression-free survival; PGL, paraganglioma; RCC, renal cell carcinoma; SD, stable disease; SSBs, single-strand breaks; TCGA, the cancer genome atlas; TGCT, testicula","cbCainLXqtEFtPGw","https://ap.wps.com/l/cbCainLXqtEFtPGw","pdf",299751,11,"English","# Abstract\n# Introduction\n## PARP biology and DNA single-strand break repair\n## Synthetic lethality in BRCA1/2-mutated tumors\n## PARPi clinical relevance and expansion to other GU cancers","[{\"question\":\"How do PARP inhibitors induce synthetic lethality in HRD tumors?\",\"answer\":\"PARPis inhibit the repair of single-strand DNA breaks, leading to replication-associated double-strand breaks and cancer cell death. HRD tumors are especially vulnerable because homologous recombination-mediated DSB repair is impaired.\"},{\"question\":\"Which PARP inhibitors are approved for BRCA1/2-mutant metastatic prostate cancer?\",\"answer\":\"Olaparib, rucaparib, and talazoparib are approved for metastatic prostate cancer patients with BRCA1/2 mutations, with some regimens also used in combination with other agents.\"},{\"question\":\"What is the review’s focus regarding biomarkers beyond BRCA1/2?\",\"answer\":\"The review examines biomarkers that predict PARPi response in genitourinary cancers beyond BRCA1/2 mutations. It also discusses the current state and future perspectives of PARPis across GU cancer types.\"}]","PARP Inhibitors in Genitourinary Cancer: A New Paradigm Beyond Prostate Cancer | PDF",1790172852,28]