ArticleThe oncologist2020
Prognostic Value of DNA Damage Response Genomic Alterations in Relapsed/Advanced Urothelial Cancer.
Article in The oncologist, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04872036 (Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens), which is not on this map. Cited by 14 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens
Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- DNA damage response pathway alterations in urothelial carcinoma: a road to precision oncology or a dead-end street?The oncologist · 2026Review
- Immune checkpoint inhibitors in bladder cancer: from mechanistic insights to emerging combination frontlines.Clinical and experimental medicine · 2026Review
- Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma.Molecules (Basel, Switzerland) · 2024Review
- New Perspectives on the Role of Liquid Biopsy in Bladder Cancer: Applicability to Precision Medicine.Cancers · 2024Review
- PRPF19 functions in DNA damage repair and gemcitabine sensitivity via regulating DDB1 in bladder cancer cells.Cytotechnology · 2024Article
- Personalized treatment with PARP inhibitors in advanced urothelial carcinoma: a case report and literature review.Therapeutic advances in medical oncology · 2024Article
- ATR Inhibition in Advanced Urothelial Carcinoma.Clinical genitourinary cancer · 2023Review
- Article
- Roles of DNA damage repair and precise targeted therapy in renal cancer (Review).Oncology reports · 2022Article
- Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer.Pathology oncology research : POR · 2022Article
- Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer.Cancer communications (London, England) · 2021Review
- Identification of a Nuclear Mitochondrial-Related Multi-Genes Signature to Predict the Prognosis of Bladder Cancer.Frontiers in oncology · 2021Article
- The interplay of cell cycle and DNA repair gene alterations in upper tract urothelial carcinoma: predictive and prognostic implications.Precision clinical medicine · 2020Article
- Current Perspectives on Immunotherapy in the Peri-Operative Setting of Muscle-Infiltrating Bladder Cancer.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA damage response (DDR) genomic alterations may play an important role in clinical outcomes of patients with urothelial cancer (UC). However, data on the prognostic role of DDR gene alterations in patients with advanced UC remain unclear. MATERIALS AND
methodsWe retrospectively collected data of three independent patient cohorts with relapsed or advanced UC including 81 and 91 patients from four institutions who underwent FoundationOne genomic sequencing as well as 129 patients selected from The Cancer Genome Atlas bladder cohort. Fisher's exact test was used to determine differences of mutation frequency among the three cohorts. Logistic regression analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI). Overall survival (OS) was measured from time of initial diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% CI.
resultsDDR genomic alterations were present in 76.5% (62/81), 40.7% (37/91), and 51.2% (66/129) of the three cohorts. ATM alterations consistently correlated with significantly shorter OS, whereas other DDR alterations (excluding ATM) were associated with better prognosis. In 152 patients treated with platinum pooled from the three cohorts, the prognostic value of alterations in ATM as compared with other predefined DDR genes was substantially different (ATM: adjusted HR [HR], 2.03; 95% CI, 1.03-4; p = .04; other DDR: adjusted HR, 0.49; 95% CI, 0.31-0.8; p = .003).
conclusionsGenomic alterations in ATM and other DDR genes may have opposite prognostic value in relapsed and/or advanced UC. ATM may have a complex role in UC progression. IMPLICATIONS FOR PRACTICE: Somatic mutations of DNA damage response (DDR) genes are frequently found in urothelial cancer and appear to play an important role in tumorigenesis, progression, treatment response, and outcomes. In a set of DDR genes, ATM alterations were associated with worse survival, while other alterations were associated with better survival in advanced urothelial cancer. The results of this study suggest a complex role of ATM in tumor progression and call for further studies to determine the underlying mechanisms and biomarker clinical utility.
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