Subtype
Urinary Tract Neoplasm
CI-CAN-00001627Explore in graph →
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Subtype
CI-CAN-00001627Explore in graph →
Variants & evidence
100 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| FGFR3 K650T1 | ||||||||
| (oncogenic) | Malignant Bladder NeoplasmALIAS | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID10492Targeted mutation analysis on the FGFR3 gene in 297 bladder cancer patients was conducted, where 177 patients were found to harbor FGFR3 mutations. Among those patients, one harbored the K650T variant… (full text at CIViC) PMID 12461689 · van Rhijn et al., 2002 · Open in CIViC | civic |
| FGFR3 Mutation4 | ||||||||
| (prognostic) | Malignant Bladder NeoplasmALIAS | Prognostic | B | Does Not Support Better Outcome | 3 | submitted | EID9258The authors screened 85 superficial bladder tumor patients (35 with early-stage (stage Ta/grade 1-2) and 50 with an advanced stage (stage T1 or grade 3)) for variants in FGFR3 and TP53 genes. FGFR3 ac… (full text at CIViC) PMID 16278391 · Zieger et al., 2005 · Open in CIViC | civic |
| Cisplatin + GemcitabineCombination | Malignant Bladder NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID7566In this study, 52 patients with Muscle Invasive Bladder Cancer (MIBC) were randomly selected and administered neoadjuvant cisplatin and gemcitabine chemotherapy. 39 out of 52 patients showed pathologi… (full text at CIViC) PMID 29941343 · Yang et al., 2018 · Open in CIViC | civic |
| Erdafitinib | ||||||||
| FGFR3 Overexpression1 | ||||||||
| Dovitinib + PD173074 + Tyrosine Kinase Inhibitor SU5402Substitutes | Bladder Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID803The effects of FGFR inhibitors (PD173074, TKI-258 and SU5402) in bladder carcinoma cell lines were related to FGFR3 (and/or FGFR1) expression. PMID 21119661 · Lamont et al., 2011 · Open in CIViC | civic |
| FGFR3 R248C3 | ||||||||
| (oncogenic) | Bladder Carcinoma | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID10387FGFR3 R248C promoted FGF1 and IL-3 independent cell proliferation when transduced into Ba/F3 cells whereas Ba/F3 cells with wildtype FGFR3 were IL-3 independent, but FGF1 dependent. PMID 19381019 · Qing et al., 2009 · Open in CIViC | civic |
| Erdafitinib | Urothelial Carcinoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID13088In a Phase 3 trial (NCT03390504), patients with metastatic or surgically unresectable urothelial carcinoma, who had FGFR2 or FGFR3 alterations erdafitinib was tested against chemotherapy (docetaxel or… (full text at CIViC) PMID 37870920 · Loriot et al., 2023 · Open in CIViC | civic |
| Infigratinib | Bladder Carcinoma | Predictive | B | Supports Sensitivity Response | 1 | submitted | ||
| FGFR3 S249C10 | ||||||||
| (oncogenic) | Bladder Urothelial Carcinoma | Oncogenic | D | Supports Oncogenicity | 4 | accepted | EID8853In contrast to controls (empty vector and FGFR3 wild-type overexpression NIH-3T3 cell lines), the stable transfection of NIH-3T3 cells with FGFR3b-S249C led to ligand-independent phosphorylation of FG… (full text at CIViC) PMID 16338952 · Bernard-Pierrot et al., 2006 · Open in CIViC | civic |
| 〃 | Bladder Carcinoma | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID10386FGFR3 S249C promoted FGF1 and IL-3 independent cell proliferation when transduced into Ba/F3 cells, whereas Ba/F3 cells with wildtype FGFR3 were IL-3 independent, but FGF1 dependent. R3Mab (monclonal … (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC | civic |
| (diagnostic) | Bladder Urothelial Carcinoma | Diagnostic | D | Supports Positive | 3 | |||
| FGFR3 G370C + FGFR3 R248C + FGFR3 S249C + FGFR3 Y373C1 | ||||||||
| Erdafitinib | Bladder Carcinoma | Predictive | A | Supports Sensitivity Response | 4 | rejected | EID11259In this open-label, phase II trial, 99 patients with locally advanced and unresectable or metastatic urothelial carcinoma with various FGFR alterations who had a history of disease progression during … (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC | civic |
| FGFR3 T450M1 | ||||||||
| (oncogenic) | Bladder Carcinoma | Oncogenic | B | Does Not Support Oncogenicity | 2 | submitted | EID12596An Asian germline dataset (jMorp-14KJPN) was analyzed and five significantly enriched non-synonymous single nucleotide polymorphisms (SNPs) on the FGFR3 gene locus were found (Q29H, G65R, L164V, T450M… (full text at CIViC) PMID 37980528 · Komura et al., 2023 · Open in CIViC | civic |
| TACC3 Fusion1 | ||||||||
| Fexagratinib | Renal Pelvis Urothelial CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID9227Phase II study (NCT02465060) from NCI-MATCH Trial (EAY131) Subprotocol W addressed the use of AZD4547 (an FGFR 1-3 inhibitor) in 48 tumor patients carrying FGFR 1-3 variants. Partial responses were ob… (full text at CIViC) PMID 32463741 · Chae et al., 2020 · Open in CIViC | civic |
| FGFR3 Fusion2 | ||||||||
| Erdafitinib | Bladder Carcinoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11258In this open-label, phase II trial, 99 patients with locally advanced and unresectable or metastatic urothelial carcinoma with various FGFR alterations who had a history of disease progression during … (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC | civic |
| 〃 | Bladder Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID10405Phase I dose-escalation cohort of patients with advanced solid tumors in which antineoplastic therapy (NCT01703481) was no longer effective using pan-FGFR inhibitor JNJ-42756493. Among 6 patients with… (full text at CIViC) PMID 31088831 · Bahleda et al., 2019 · Open in CIViC | civic |
| FGFR3 Y373C8 | ||||||||
| (diagnostic) | Bladder Carcinoma | Diagnostic | B | Supports Positive | 3 | accepted | EID477Y375C mutation results in activation of FGFR3 and is associated with bladder carcinoma. Patients with low-grade tumors were more likely to have FGFR3 mutations than those with high-grade tumors. PMID 20542753 · Bodoor et al., 2010 · Open in CIViC | civic |
| (oncogenic) | Malignant Bladder NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | accepted | EID8880Using site-directed mutagenesis, the authors investigated the phenotypic and signaling consequences of three FGFR3 mutations, S249C, Y373C (in the paper described as Y375C), and K652E, in immortalized… (full text at CIViC) PMID 19749790 · di Martino et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Bladder NeoplasmALIAS | Oncogenic | D | |||||
| FGFR3 N540K + FGFR3 Y373C1 | ||||||||
| Erdafitinib + FutibatinibSequential | Urothelial Carcinoma | Predictive | C | Supports Resistance | 4 | accepted | EID12704In this study of patients with FGFR-driven urothelial carcinoma treated with selective FGFR inhibitors, longitudinal ctDNA analysis identified emergent FGFR3 kinase domain mutations at disease progres… (full text at CIViC) PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC | civic |
| GNAS c.393T>C1 | ||||||||
| (prognostic) | Bladder Urothelial Carcinoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID2892This study demostrated that the progression-free survival, metastasis-free survival, and cancer-specific survival was significantly increased in patients with T393 homozygosity i.e. TT genotypes (56%,… (full text at CIViC) PMID 15824158 · Frey et al., 2005 · Open in CIViC | civic |
| HRAS Mutation1 | ||||||||
| Tipifarnib | Bladder Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID96324 of 16 patients with urothelial carcinoma harboring HRAS hotspot point mutations and 1 patient with an HRAS frameshift insertion had a partial response to the farnesyltransferase inhibitor tipifarnib… (full text at CIViC) PMID 32636318 · Lee et al., 2020 · Open in CIViC | civic |
| KDM6A Loss1 | ||||||||
| EZH2 Inhibitor | Malignant Bladder NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID11749In this study, an EZH2 inhibitor was tested for effectiveness against KDM6A-null cancer in mouse and patient-derived xenografts. The growth of KDM6A null tumours was significantly inhibited in the in … (full text at CIViC) PMID 28228601 · Ler et al., 2017 · Open in CIViC | civic |
| KMT2C Loss-of-function1 | ||||||||
| Olaparib | Bladder Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12773In preclinical xenograft models derived from KMT2C-deficient tumors (HTB9 BC, H1437 NSCLC, T84 COAD, Cal-33 HNSCC), PARP1/2 inhibition with olaparib significantly reduced tumor growth compared to KMT2… (full text at CIViC) PMID 30665945 · Rampias et al., 2019 · Open in CIViC | civic |
| KMT2C Loss-of-function + KMT2D Loss-of-functionKMT2DKMT2C1 | ||||||||
| Afatinib + GefitinibSubstitutes | Urothelial Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12775In preclinical urothelial carcinoma (UC) models, combined loss of KMT2C/KMT2D increased sensitivity to EGFR inhibitors, with Kmt2c/d-deficient cells showing significantly reduced IC50 values for afati… (full text at CIViC) PMID 39806204 · Wang et al., 2025 · Open in CIViC | civic |
| MTAP Deletion1 | ||||||||
| Pemetrexed | Bladder Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID12722In a single-arm phase II trial of pemetrexed in previously treated metastatic urothelial carcinoma selected for MTAP deficiency by IHC (NCT02693717; n = 7), 3 patients (42%) achieved ORR, with median … (full text at CIViC) PMID 35379845 · Alhalabi et al., 2022 · Open in CIViC | civic |
| MTOR Mutation1 | ||||||||
| Everolimus + PazopanibCombination | Bladder Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID705A case-study of a patient with urothelial carcinoma reported exceptional response (14 months) in a phase 1 study of Everolimus and Pazopanib. Mutations E2014K and E2419K were shown to be activating in… (full text at CIViC) PMID 24625776 · Wagle et al., 2014 · Open in CIViC | civic |
| FGFR3 N540K + FGFR3 S249C + PIK3CA E545KPIK3CAFGFR31 | ||||||||
| Erdafitinib | Urothelial Carcinoma | Predictive | C | Supports Resistance | 4 | accepted | EID12703In this study of 21 patients with FGFR-driven urothelial carcinoma treated with selective FGFR inhibitors (including erdafitinib), post-progression molecular analyses (tissue and/or ctDNA sequencing) … (full text at CIViC) PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC | civic |
| PTEN Loss1 | ||||||||
| Everolimus | Bladder Carcinoma | Predictive | B | Supports Resistance | 4 | accepted | EID644PTEN loss is associated with reduced response to mTOR inhibitors in patients with bladder cancer. PMID 23989949 · Seront et al., 2013 · Open in CIViC | civic |
| RAD50 L1237F1 | ||||||||
| Checkpoint Kinase Inhibitor AZD7762 + IrinotecanCombination | Ureter Small Cell Neuroendocrine CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID5829A 51-year-old woman with an invasive small-cell cancer of the ureter showed a durable complete response at 3-years when treated with AZD7762 (an ATP-competitive checkpoint kinase inhibitor) and irinot… (full text at CIViC) PMID 24934408 · Al-Ahmadie et al., 2014 · Open in CIViC | civic |
| RAF1 Amplification1 | ||||||||
| B-Raf/VEGFR-2 Inhibitor RAF265 + TrametinibCombination | Bladder Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11767In this pre-clinical study, RAF inhibition and RAF inhibition in combination with MEK inhibition was tested in vivo in RAF1-amplified tumors (in both mice and PDX tumor models). The models were treate… (full text at CIViC) PMID 34554931 · Bekele et al., 2021 · Open in CIViC | civic |
| RB1 IVS20, A-G, -21 | ||||||||
| (prognostic) | Malignant Bladder NeoplasmALIAS | Prognostic | D | Supports N/A | 4 | submitted | EID7231We have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. Our analysis indicates that inactivation of the … (full text at CIViC) PMID 2181449 · Horowitz et al., 1990 · Open in CIViC | civic |
| STAG2 Underexpression1 | ||||||||
| (prognostic) | Bladder Carcinoma | Prognostic | B | Supports Better Outcome | 2 | accepted | EID984Tumor samples from 125 patients with bladder cancer were assessed by IHC for STAG2 expression. STAG2-negativity was associated with lower histological grade (p = 0.009). Complete loss of STAG2 express… (full text at CIViC) PMID 26838030 · Qiao et al., 2016 · Open in CIViC | civic |
| TERT Promoter Mutation1 | ||||||||
| (prognostic) | Bladder Urothelial Carcinoma | Prognostic | B | Supports Better Outcome | 4 | submitted | EID7968Patients with mutations at TERT promoter region of -124 and -146 of ATG showed poor survival in the absence but not in the presence of the variant allele of a common polymorphism with ID of rs2853669 … (full text at CIViC) PMID 24101484 · Rachakonda et al., 2013 · Open in CIViC | civic |
| High1 | ||||||||
| Immunotherapy | Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID13302This is a retrospective cohort study examining the association between tumour mutational burden (TMB) and clinical benefit from first-line single-arm immune checkpoint inhibitor (ICPI) therapy compare… (full text at CIViC) PMID 35977348 · Graf et al., 2022 · Open in CIViC | civic |
| TSC1 Frameshift Truncation1 | ||||||||
| Everolimus | Invasive Bladder Urothelial CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID320A patient with metastatic bladder cancer that responded well to the mTOR inhibitor everolimus was shown to harbor a TSC1 frameshift truncation mutation (c.1907_1908del, p.Glu636fs) and a nonsense NF2 … (full text at CIViC) PMID 22923433 · Iyer et al., 2012 · Open in CIViC | civic |
| TSC1 Loss-of-function1 | ||||||||
| Everolimus | Bladder Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID155Tumors (n=14) expressing TSC1 mutations (5/14) show notably more sensitivity to everolimus than their wild-type counterparts (9/14). A dramatic response was observed in a patient with combination of L… (full text at CIViC) PMID 22923433 · Iyer et al., 2012 · Open in CIViC | civic |
Data updated 16 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Predictive |
| B |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID10397Phase I dose-escalation cohort (NCT01703481) of patients with advanced solid tumors in which antineoplastic therapy was no longer effective using pan-FGFR inhibitor JNJ-42756493. All 16 patients with … (full text at CIViC) PMID 31088831 · Bahleda et al., 2019 · Open in CIViC |
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| Infigratinib | Bladder Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1910Phase 1 study evaluated 132 patients who had advanced cancer with FGFR-aberrations treated with FGFR-inhibitor BGJ398. In the subgroup of eight patients with FGFR3-mutated bladder/urothelial cancer tr… (full text at CIViC) PMID 27870574 · Nogova et al., 2017 · Open in CIViC | civic |
Phase 2 BGJ398 dose escalation to determine maximum tolerated dose and RP2D dose. There was Antitumor activity PR in FGFR3-mutant bladder/urothelial carcinoma.
PMID 27870574 · Nogova et al., 2017 · Open in CIViC
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| submitted |
EID8668Activating FGFR3 mutations are found more frequently in lower grade / early stage urothelial carcinoma. FGFR mutations are also associated with high FGFR3 expression. FGFR3 expression therefore demons… (full text at CIViC) PMID 16532037 · Lindgren et al., 2006 · Open in CIViC |
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| AZD-4547 | Renal Pelvis Urothelial CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID8316The phase II NCI-MATCH trial (EAY131) subprotocol W assessed the FGFR1-3 selective TKI AZD-4547 in 48 patients with FGFR1/2 amplifications, FGFR2/3 SNV or FGFR1/3 fusions. The partial response overall… (full text at CIViC) PMID 32463741 · Chae et al., 2020 · Open in CIViC | civic |
| Erdafitinib | Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12953In a retrospective cohort of 32 patients with metastatic urothelial carcinoma harboring FGFR2/3 alterations treated with erdafitinib, FGFR3 S249C was the most common alteration (19/32, 59%). The overa… (full text at CIViC) PMID 37682528 · Guercio et al., 2023 · Open in CIViC | civic |
| 〃 | Bladder Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID12955This report describes a patient with metastatic urothelial bladder cancer harboring an FGFR3 S249C mutation who developed disease progression after platinum-based chemotherapy and avelumab maintenance… (full text at CIViC) PMID 37343207 · Castro-Alonso et al., 2023 · Open in CIViC | civic |
| 〃 | Malignant Bladder NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID8811The 97-7 bladder cancer cell line is heterozygous for FGFR3 S249C, which formed stable homodimers and was constitutively phosphorylated unlike WT FGFR3 found in NHUC cells. Retrovirus-mediated deliver… (full text at CIViC) PMID 17384684 · Tomlinson et al., 2007 · Open in CIViC | civic |
| Erdafitinib + QuisinostatCombination | Malignant Bladder NeoplasmALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12954This preclinical study evaluated the combination of erdafitinib and quisinostat in bladder cancer models harboring FGFR3 alterations, including the FGFR3 S249C bladder cancer cell line UM-UC-14. Compa… (full text at CIViC) PMID 37479885 · Wang et al., 2023 · Open in CIViC | civic |
| Futibatinib | Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11635In a phase 1 multihistology trial of the FGFR1/2/3/4 inhibitor futibatinib, an objective response rate of 13.7% was seen with responses in a broad spectrum of tumors and across a broad spectrum of FGF… (full text at CIViC) PMID 34551969 · Meric-Bernstam et al., 2022 · Open in CIViC | civic |
| R3Mab | Bladder Carcinoma | Predictive | D | Does Not Support Resistance | 3 | rejected | EID9088In a preclinical experiment, R3Mab (a monoclonal antibody specific to FGFR3) was tested against Ba/F3 and bladder carcinoma cell lines expressing FGFR3 wildtype and FGFR3 variants prevalent in bladder… (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC | civic |
| 3 |
| accepted |
EID8881The authors identified a bladder cancer cell line (MGH-U3) with a homozygous Y373C mutation. With immunoprecipitation (IP), and immunoblotting (IB) experiments, they demonstrated constitutional phosph… (full text at CIViC) PMID 16338952 · Bernard-Pierrot et al., 2006 · Open in CIViC |
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| Erdafitinib | Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13203In a bridging analysis of the phase 2 BLC2001 study of patients with metastatic or locally advanced, surgically unresectable urothelial carcinoma harboring FGFR alterations, 11 patients with FGFR3 Y37… (full text at CIViC) PMID 32304281 · Wang et al., 2020 · Open in CIViC | civic |
| 〃 | Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13204In a randomized controlled phase 3 trial, patients with FGFR2 or FGFR3 alterations including Y373C treated with erdafitinib vs standard chemotherapy were found to have increased overall survival (12.… (full text at CIViC) PMID 37870920 · Loriot et al., 2023 · Open in CIViC | civic |
| 〃 | Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13205In a phase 2 trial of patients with advanced or metastatic urothelial cancer who were positive for FGFR2 fusions or known FGFR3 variants (including Y373C), 40% of patients showed an objective response… (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC | civic |
| 〃 | Urothelial Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13206In a Phase III randomized controlled trial, 351 patients with metastatic or advanced urothelial cancer with qualifying FGFR2 or FGFR3 alterations (including FGFR3 Y373C) were treated with pembrolizuma… (full text at CIViC) PMID 37871702 · Siefker-Radtke et al., 2024 · Open in CIViC | civic |
| 〃 | Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID13212In a study of 32 patients with metastatic urothelial carcinoma who were treated with erdafitinib, tumor genomic sequencing was done using FDA-authorized MSK-IMPACT. 3 patient had FGFR3 Y373C. All thre… (full text at CIViC) PMID 37682528 · Guercio et al., 2023 · Open in CIViC | civic |