Subtype
Urinary System Carcinoma
CI-CAN-00004182Explore in graph →
- NCIt
- C181197
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Subtype
CI-CAN-00004182Explore in graph →
Variants & evidence
294 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 |
|---|---|---|---|---|---|---|---|---|
| FBXW7 Loss-of-function1 | ||||||||
| Everolimus | Renal Cell CarcinomaCURATED_BROADER | Predictive | E | Supports Sensitivity Response | 2 | accepted | EID1628mTOR protein levels were found to underly a circadian 24-hour rhythm regulated by time-dependent Fbxw7-mediated ubiquitination. Survival rates of tumor-bearing mice with everolimus showed time-depende… (full text at CIViC) PMID 24253377 · Okazaki et al., 2014 · Open in CIViC | civic |
| FGFR1 Amplification1 | ||||||||
| Infigratinib | Bladder Carcinoma | Predictive | C | Does Not Support Sensitivity Response | 2 | accepted | EID1911Phase 1 study of FGFR-inhibitor BGJ398 in advanced cancer with FGFR-aberrations. Of the eight patients with FGFR3-mutated bladder/urothelial cancer, one patient with FGFR1 amplification was treated wi… (full text at CIViC) PMID 27870574 · Nogova et al., 2017 · Open in CIViC | civic |
| FGFR1 Expression2 | ||||||||
| Unspecified therapy | Bladder Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | rejected | EID802FGFR1 expression was increased in urothelial carcinoma cell lines and patient tumours, independent of stage and grade. FGFR1 knockdown resulted in decreases proliferation and survival in some of the c… (full text at CIViC) PMID 19458078 · Tomlinson et al., 2009 · Open in CIViC | civic |
| Dovitinib + PD173074Substitutes | Bladder Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID801One urothelial cell line (JMSU1) with high expression of FGFR1 was sensitive to treatment with FGFR inhibitors (SU5402, TKI258 or PD173074). IC50 values for PD173074 and TKI-258 (Dovitinib) were in n… (full text at CIViC) PMID 21119661 · Lamont et al., 2011 · Open in CIViC | civic |
| FGFR1 M563T1 | ||||||||
| Futibatinib | Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID11636In 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 |
| FGFR1 Overexpression1 | ||||||||
| (prognostic) | Bladder Urothelial Carcinoma | Prognostic | D | Supports Poor Outcome | 4 | submitted | EID9582Two types of UC cell lines were compared in this study. T24 and J82 which are mesenchymal subtype and overexpress FGFR1, and RT-4 and UMUC-14, epithelial subtype which do not express FGFR1. T24 and J8… (full text at CIViC) PMID 30326563 · Kim et al., 2018 · Open in CIViC | civic |
| FGFR2 Fusion1 | ||||||||
| Erdafitinib | Bladder Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID10404Phase 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 2 urothelial ca… (full text at CIViC) PMID 31088831 · Bahleda et al., 2019 · Open in CIViC | civic |
| FGFR2 Overexpression1 | ||||||||
| (prognostic) | Papillary Renal Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID6454Only 12/118(10.2%) of patients with type I papillary renal cell carcinoma expressed FGFR2 whereas 37/96 (38.5%) patients with type II papillary renal cell carcinoma(P=0.001). In addition, FGFR2 expre… (full text at CIViC) PMID 27379982 · Tsimafeyeu et al., 2017 · Open in CIViC | civic |
| FGFR2 Fusion1 | ||||||||
| Erdafitinib | Bladder Carcinoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11257In 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 |
| BAIAP2L1 Fusion1 | ||||||||
| PD173074 | Bladder Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID144Following identification of this fusion in a patient, this fusion was expressed in HEK 293T cells leading to oligomerization in the absence of ligand, induced morphologic changes in the cell and incre… (full text at CIViC) PMID 23558953 · Wu et al., 2013 · Open in CIViC | civic |
| FGFR3 G370C4 | ||||||||
| (oncogenic) | Bladder Urothelial Carcinoma | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID13142In a pan-cancer analysis of 10,967 TCGA tumor samples across 32 cancer types, FGFR3 G370C was identified in 5 bladder urothelial carcinoma samples and was classified as an oncogenic FGFR3 mutation. G3… (full text at CIViC) PMID 34160364 · Li et al., 2021 · Open in CIViC | civic |
| 〃 | Bladder Urothelial Carcinoma | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID13144In an analysis of TCGA bladder urothelial carcinoma, somatic FGFR3 G370C was recurrently identified in 3 independent tumor samples, all within the non-T-cell-inflamed subgroup. The authors described G… (full text at CIViC) PMID 27197067 · Sweis et al., 2016 · Open in CIViC | civic |
| Erdafitinib | Urothelial Carcinoma | Predictive | A | Supports Sensitivity Response | 4 | |||
| FGFR3 K508M1 | ||||||||
| (oncogenic) | Bladder Carcinoma | Oncogenic | D | Does Not Support Oncogenicity | 2 | submitted | EID11803The study found that TGFβ-activated kinase 1 (TAK1) is a novel protein that interacts and is targeted by FGFR3 kinase activity. Activating mutations in FGFR3 modulate expression of genes that regulate… (full text at CIViC) PMID 24466111 · Salazar et al., 2014 · Open in CIViC | civic |
| FGFR3 Mutation2 | ||||||||
| Erdafitinib | Bladder Urothelial Carcinoma | 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 | civic |
| 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 |
| 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 S249C8 | ||||||||
| (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 Y373C6 | ||||||||
| (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 |
| 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 | ||
| 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 |
| FH Deficient2 | ||||||||
| Bevacizumab + ErlotinibCombination | Hereditary Renal Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12939In the open‑label phase II AVATAR trial (NCT01130519), patients with HLRCC‑associated papillary RCC harboring germline FH pathogenic variants (n = 43) received erlotinib plus bevacizumab, with ORR as … (full text at CIViC) PMID 40532152 · Srinivasan et al., 2025 · Open in CIViC | civic |
| 〃 | Papillary Renal Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12940In the open‑label phase II AVATAR trial (NCT01130519), patients with sporadic papillary RCC (n = 40) received erlotinib plus bevacizumab, with ORR as the primary endpoint. They demonstrated a lower OR… (full text at CIViC) PMID 40532152 · Srinivasan et al., 2025 · Open in CIViC | civic |
| FLCN c.1285dupC1 | ||||||||
| Everolimus | Renal Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID10137A case study showed that the mTOR inhibitor everolimus exhibited a relatively long-term effect in a patient with renal cell carcinoma and a FLCN germline mutation (c. 1285dupC, likely loss of function… (full text at CIViC) PMID 23995526 · Nakamura et al., 2013 · Open in CIViC | civic |
| FLCN Loss1 | ||||||||
| Sirolimus | Kidney CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5991Genetic disruption of Flcn in mouse kidney distal tubule cells leads to tumorigenic transformation of these cells to develop allograft tumors with an aggressive histologic phenotype. mTOR pathway play… (full text at CIViC) PMID 26418749 · Wu et al., 2015 · Open in CIViC | civic |
| FLCN Mutation1 | ||||||||
| Everolimus | Papillary Renal Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID5990In a patient with Birt-Hogg-Dubé syndrome-associated papillary renal cell carcinoma use of everolimus as sixth-line systematic treatment exhibited a relatively long-term effect as compared with the pr… (full text at CIViC) PMID 23995526 · Nakamura et al., 2013 · Open in CIViC | civic |
| FLT3 T227M1 | ||||||||
| Sunitinib | Renal Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Adverse Response | 3 | accepted | EID1317In 219 patients with mostly Renal Cell Carcinoma and some Gastrointestinal Stromal tumors given sunitinib treatment, FLT3 T227M (rs1933437) was associated with the development of leukopenia. 95% confi… (full text at CIViC) PMID 19667267 · van Erp et al., 2009 · Open in CIViC | civic |
| GNAS c.393T>C2 | ||||||||
| (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 |
| 〃 | Clear Cell Renal Cell Carcinoma | Prognostic | B | Supports Better Outcome | 4 | accepted | EID2896In this study, Kaplan-Meier curves for tumor progression, development of metastasis, and tumor-related death showed a significant association of the T393C polymorphism with outcome (5-year cancer-spec… (full text at CIViC) PMID 16467086 · Frey et al., 2006 · Open in CIViC | civic |
| HBB E6V1 | ||||||||
| (predisposing) | SMARCB1-Deficient Kidney Medullary CarcinomaALIAS | Predisposing | B | Supports Predisposition | 2 | submitted | EID11166In a retrospective analysis of 20 patients with renal medullary carcinoma, all patients were found to have sickle cell trait (a condition due to a germline mutation in hemoglobin B known as HBB E6V), … (full text at CIViC) PMID 30980040 · Jia et al., 2019 · Open in CIViC | civic |
Data updated 9 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.
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EID13179In the randomized phase III THOR Cohort 1 trial of patients with advanced or metastatic urothelial carcinoma harboring selected FGFR alterations, FGFR3 G370C was a prespecified qualifying alteration. … (full text at CIViC) PMID 37870920 · Loriot et al., 2023 · Open in CIViC |
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| 〃 | Urothelial Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID13176In a bridging analysis of the phase 2 BLC2001 study of patients with metastatic or locally advanced, surgically unresectable urothelial carcinoma harboring FGFR alterations, 3 erdafitinib-treated pati… (full text at CIViC) PMID 32304281 · Wang et al., 2020 · 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 |
| 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 |
In 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
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| 〃 | 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 |