{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:10:17Z","timestamp":1788977417316,"version":"build-2803163510"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Urothelial carcinoma ranks among the most common solid tumors and exhibits aggressive behavior, with limited survival in the metastatic setting despite recent therapeutic advances. Currently, 3 first-line systemic treatment options are supported by level IA evidence, yet no validated predictive biomarkers exist to guide selection among them. Alterations in DNA damage response (DDR) pathways occur in a substantial proportion of urothelial tumors and have emerged as potential predictive biomarkers of treatment sensitivity. This review examines the biological basis of DDR pathways and their implications in carcinogenesis, summarizes the frequency and spectrum of DDR gene alterations in urothelial carcinoma, and critically appraises the available evidence linking these alterations to responses to platinum-based chemotherapy, immune checkpoint inhibitors, and PARP inhibitors in both muscle-invasive and metastatic settings. Although retrospective data suggest associations between DDR alterations and improved outcomes with certain therapies, results across studies are heterogeneous, likely reflecting inconsistent definitions of DDR alterations, the variable functional impact of individual mutations, and differences in patient populations. We discuss these limitations and highlight the need for standardized criteria and prospective validation to determine whether DDR pathway alterations can be reliably integrated into clinical decision-making for patients with urothelial carcinoma.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag284","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:55:14Z","timestamp":1784807714000},"source":"Crossref","is-referenced-by-count":0,"title":["DNA damage response pathway alterations in urothelial carcinoma: a road to precision oncology or a dead-end street?"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2904-3699","authenticated-orcid":false,"given":"Patricia","family":"Guerrero Serrano","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Sotoca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7769-8569","authenticated-orcid":false,"given":"Adriana","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Gonz\u00e1lez-Merino","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-9653","authenticated-orcid":false,"given":"Coral Garc\u00eda","family":"de Quevedo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-8174","authenticated-orcid":false,"given":"Jos\u00e9 Daniel","family":"Subiela","sequence":"additional","affiliation":[{"name":"Department of Urology, Ram\u00f3n y Cajal University Hospital , M-607, Km. 9, 100, Fuencarral-El Pardo , Madrid 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Bueno","sequence":"additional","affiliation":[{"name":"Department of Urology, Infanta Sof\u00eda Hospital , Paseo Europa, 34, San Sebasti\u00e1n de los Reyes , Madrid 28702,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-2551","authenticated-orcid":false,"given":"V\u00edctor","family":"Albarr\u00e1n","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapies Group, Cell Therapy Unit, Clinic Barcelona Comprehensive Cancer Center, IDIBAPS , Carrer de Villarroel, 170 , Barcelona 08036,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurea","family":"Molina","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Complejo Hospitalario Universitario de La Coru\u00f1a , 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