{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T20:29:34Z","timestamp":1779395374656,"version":"3.53.1"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Niraparib, a poly ADP-ribose polymerase inhibitors (PARPi), has been widely applied in the intervention of epithelial ovarian, fallopian tube, or primary peritoneal cancer. Nevertheless, as of the present moment, there are limited instances demonstrating favorable outcomes stemming from niraparib therapy in patients with clear cell renal cell carcinoma (ccRCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>Here, we report a case of a 50-year-old patient with ccRCC who subsequently developed distant metastasis. The patient received monotherapy with pazopanib and combination therapy with axitinib and tislelizumab, demonstrating limited efficacy. Liquid biopsy revealed missense mutations in the <jats:italic>CDK12<\/jats:italic> and <jats:italic>RAD51C<\/jats:italic> of the homologous recombination repair (HRR) pathway, suggesting potential sensitivity to PARPi. Following niraparib treatment, the patient\u2019s condition improved, with no significant side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, patients with ccRCC harboring HRR pathway gene mutation may potentially benefit from niraparib. This will present more options for ccRCC patients with limited response to conventional treatments.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1396606","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T04:59:13Z","timestamp":1718600353000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Niraparib for the treatment of metastatic ccRCC in a patient with CDK12 and RAD51C mutations: a case report"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiaolong","family":"Yue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenkang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.2217\/fon-2023-0550","article-title":"Determining magnitude of benefit from poly (ADP-ribose) polymerase inhibitors in prostate cancer","volume":"19","author":"Akb\u0131y\u0131k","year":"2023","journal-title":"Future Oncol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s10637-019-00867-4","article-title":"Veliparib in ovarian cancer: a new synthetically lethal therapeutic approach","volume":"38","author":"Boussios","year":"2020","journal-title":"Investig. new drugs"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5690","DOI":"10.1158\/1538-7445.am2022-5690","article-title":"Abstract 5690: the landscape of homologous recombination repair gene mutations and prognosis in Chinese patients with clear cell renal cell carcinoma","volume":"82","author":"Chen","year":"2022","journal-title":"Cancer Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.46439\/cancerbiology.4.049","article-title":"PARP inhibitors in HRD BRCAness breast cancer patients","volume":"4","author":"Eiriz","year":"2023","journal-title":"J. Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41591-023-02704-x","article-title":"First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial","volume":"30","author":"Fizazi","year":"2023","journal-title":"Nat. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"17009","DOI":"10.1038\/nrdp.2017.9","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B7","doi-asserted-by":"publisher","first-page":"587","DOI":"10.6004\/jnccn.2019.5008","article-title":"NCCN guidelines updates: management of metastatic kidney cancer","volume":"17","author":"Jonasch","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4257","DOI":"10.1158\/1078-0432.CCR-15-0887","article-title":"FDA approval summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy","volume":"21","author":"Kim","year":"2015","journal-title":"Clin. cancer Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1038\/s41467-019-09703-y","article-title":"CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation","volume":"10","author":"Krajewska","year":"2019","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3892\/or.2022.8428","article-title":"Roles of DNA damage repair and precise targeted therapy in renal cancer","volume":"48","author":"Lai","year":"2022","journal-title":"Oncol. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.semcancer.2018.06.004","article-title":"Challenges and opportunities in the proteomic characterization of clear cell renal cell carcinoma (ccRCC): a critical step towards the personalized care of renal cancers","volume":"55","author":"Li","year":"2019","journal-title":"Seminars cancer Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"927250","DOI":"10.3389\/fonc.2022.927250","article-title":"Clinical benefit of Niraparib to TKI\/mTORi-resistance metastatic ccRCC with BAP1-frame shift mutation: case report and literature review","volume":"12","author":"Lian","year":"2022","journal-title":"Front. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1517\/13543784.2012.707189","article-title":"Olaparib, PARP1 inhibitor in ovarian cancer","volume":"21","author":"Marchetti","year":"2012","journal-title":"Expert Opin. investigational drugs"},{"key":"B14","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1158\/1535-7163.MCT-12-0950","article-title":"RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib","volume":"12","author":"Min","year":"2013","journal-title":"Mol. cancer Ther."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e445","DOI":"10.1016\/j.clgc.2016.03.012","article-title":"Novel use of targeted therapy via PARP-inhibition in a rare form of papillary renal cell carcinoma: a case report and literature review","volume":"14","author":"Olson","year":"2016","journal-title":"Clin. Genitourin. Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"681441","DOI":"10.3389\/fonc.2021.681441","article-title":"The emerging role of poly (ADP-Ribose) polymerase inhibitors as effective therapeutic agents in renal cell carcinoma","volume":"11","author":"Pletcher","year":"2021","journal-title":"Front. Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1517\/14656566.2013.832202","article-title":"Targeting angiogenesis in renal cell carcinoma","volume":"14","author":"Posadas","year":"2013","journal-title":"Expert Opin. Pharmacother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1056\/NEJMoa1706450","article-title":"Olaparib for metastatic breast cancer in patients with a germline BRCA mutation","volume":"377","author":"Robson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA a cancer J. Clin."},{"key":"B20","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.urology.2021.04.025","article-title":"ATR and BRCA2 simultaneous mutation in a ccRCC with sarcomatoid differentiation and extensive metastases: a case report","volume":"154","author":"Yang","year":"2021","journal-title":"Urology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1133832","DOI":"10.3389\/fonc.2023.1133832","article-title":"Treatment strategies for clear cell renal cell carcinoma: past, present and future","volume":"13","author":"Yang","year":"2023","journal-title":"Front. Oncol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1396606\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T04:59:18Z","timestamp":1718600358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1396606\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":21,"alternative-id":["10.3389\/fphar.2024.1396606"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1396606","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,17]]},"article-number":"1396606"}}