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BIOMARKER:

FGFR3 mutation

i
Other names: FGFR3, ACH, CD333, CEK2, JTK4, Fibroblast growth factor receptor 3
Entrez ID:
2d
Dysregulated FGFR3 signaling alters the immune landscape in bladder cancer and presents therapeutic possibilities in an agent-based model. (PubMed, Front Immunol)
These results indicate the need to quantify FGFR3 signaling and the fitness advantage conferred on bladder cancer cells harboring this mutation. This ABM approach may enable rationally designed treatment plans to improve clinical outcomes.
Journal • PD(L)-1 Biomarker • IO biomarker
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FGFR3 (Fibroblast growth factor receptor 3) • CD8 (cluster of differentiation 8)
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FGFR3 mutation
4d
A deep-learning workflow to predict upper tract urothelial carcinoma protein-based subtypes from H&E slides supporting the prioritization of patients for molecular testing. (PubMed, J Pathol Clin Res)
Testing of the DL model on an independent cohort highlighted the importance to accommodate histological subtypes. Taken together, our DL workflow can predict protein-based UTUC subtypes, associated with the presence of targetable alterations, directly from H&E slides.
Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • FOXA1 (Forkhead Box A1) • GATA3 (GATA binding protein 3)
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PD-L1 expression • FGFR3 mutation
4d
Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial. (PubMed, Mol Cancer)
Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.
Journal
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FGFR3 (Fibroblast growth factor receptor 3) • TERT (Telomerase Reverse Transcriptase) • ONECUT2 (One Cut Homeobox 2)
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FGFR3 mutation • TERT mutation
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UroVysion™ Bladder Cancer Kit (UroVysion Kit)
4d
Clinical characteristics and prognosis of newly diagnosed multiple myeloma patients with FGFR3 gene mutations (PubMed, Zhonghua Xue Ye Xue Za Zhi)
The Cox proportional hazards model identified FGFR3 mutation as an independent risk factor for PFS and OS. FGFR3 gene mutation was an unfavorable independent prognostic predictor for NDMM.
Journal
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FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation
7d
FOENIX-CCA2: A Study of TAS-120 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=407, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed
Trial completion • Metastases
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 fusion • FGFR3 mutation • FGFR fusion • FGFR2 rearrangement • FGFR3 fusion
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Lytgobi (futibatinib)
1m
Integration of CD4+ T cells and molecular subtype predicts benefit from PD-L1 blockade in muscle-invasive bladder cancer. (PubMed, Cancer Sci)
These subtypes include luminal CD4+ Thigh , which demonstrated benefits from both immunotherapy and chemotherapy; luminal CD4+ Tlow , characterized by the highest level of fibroblast growth factor receptor 3 (FGFR3) mutation, thus indicating potential responsiveness to FGFR inhibitors; basal CD4+ Thigh , which could benefit from a combination of ICB and chemotherapy; and basal CD4+ Tlow , characterized by an immune suppression microenvironment and likely to benefit from transforming growth factor-β (TGF-β) inhibition. This immune-molecular classification offers new possibilities for optimizing therapeutic interventions in MIBC.
Journal • PD(L)-1 Biomarker • IO biomarker
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FGFR3 (Fibroblast growth factor receptor 3) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1)
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FGFR3 mutation
1m
Artificial Intelligence (AI) Assisted Detection of FGFR3 Alterations In Bladder Cancer From Scanned Whole Slide Images (WSI) of H&E Sections (USCAP 2024)
We developed an effective AI system for detecting phenotypes associated with FGFR3 abnormalities that may be targetable by FGFR inhibitors. This system may allow cost and time savings in comparison to existing assays to screen bladder carcinomas for additional diagnostic testing.
FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)
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FGFR3-TACC3 fusion • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 R248C
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MSK-IMPACT
1m
BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder (clinicaltrials.gov)
P=N/A, N=4, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date
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FGFR3 mutation • FGFR3 fusion
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Truseltiq (infigratinib)
2ms
Profiling Fibroblast Growth Factor Receptor 3 Expression Based on the Immune Microenvironment in Upper Tract Urothelial Carcinoma. (PubMed, Eur Urol Oncol)
Although most patients exhibit a poor response to Pem, individuals with low FGFR3 expression and immune hot status may benefit clinically from Pem treatment.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • CD8 (cluster of differentiation 8) • CD163 (CD163 Molecule) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule) • MSR1 (Macrophage Scavenger Receptor 1)
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FGFR3 mutation • CD8-H • FGFR3 expression • CD4 expression
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Keytruda (pembrolizumab)
2ms
FGFR inhibition augments anti-PD-1 efficacy in murine FGFR3-mutant bladder cancer by abrogating immunosuppression. (PubMed, J Clin Invest)
Combined erdafitinib and ICI resulted in high therapeutic efficacy. In aggregate, our work establishes that, in mice, co-alteration of FGFR3 and Trp53 results in high-grade, non-muscle-invasive UC and presents a previously underappreciated role for FGFR inhibition in blocking ICI-induced Treg expansion.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3)
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TP53 mutation • FGFR3 mutation
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Balversa (erdafitinib)
3ms
Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. (PubMed, Histopathology)
TACSTD2/TROP2 and NECTIN-4/NECTIN-4 are widely expressed in aUC, independent of FGFR3 alterations or PD-L1 expression, thus representing a suitable target for ADC treatment in the majority of aUC. The expression loss was associated with aggressive morphomolecular aUC subtypes, i.e. neuroendocrine(-like) and sarcomatoid aUC.
Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • NECTIN4 (Nectin Cell Adhesion Molecule 4) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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PD-L1 expression • FGFR3 mutation • NECTIN4 expression • FGFR3 expression
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Trodelvy (sacituzumab govitecan-hziy) • Padcev (enfortumab vedotin-ejfv)
3ms
Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy. (PubMed, Cancer Res Treat)
According to our comprehensive analysis, HG non-invasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Non-invasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.
Journal
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FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog)
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FGFR3 mutation • HRAS mutation
3ms
Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population. (PubMed, Head Neck)
In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.
Journal
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FGFR3 (Fibroblast growth factor receptor 3) • KMT2A (Lysine Methyltransferase 2A) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • KDM5C (Lysine Demethylase 5C)
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FGFR3 mutation
4ms
Real world experience of FGFR gene alterations and clinical outcomes in advanced/metastatic urothelial cancer in Japan: MONSTAR-SCREEN database study. (ASCO-GU 2024)
The results showed a similar trend to previous studies, where FGFR GA was reported in approximately 20% of metastatic UC patients. No difference was found in the PFS and the estimated survival rate by FGFR2/3 GA-positive or -negative patients. Our data showed that treatment pressure did not alter the FGFR status commonly.
Real-world evidence • Clinical data • Clinical • BRCA Biomarker • Real-world • Metastases
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TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • ARID1A (AT-rich interaction domain 1A) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • BICC1 (BicC Family RNA Binding Protein 1) • BAIAP2L1 (BAI1 associated protein 2 like 1) • BAIAP2 (BAR/IMD Domain Containing Adaptor Protein 2) • CASP7 (Caspase 7)
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FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 G370C • FGFR3 R248C
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FoundationOne® Liquid CDx
4ms
Comparison of tissue based FGFR mutation detection by Therascreen FGFR with UroTyper FGFR and ADC test and relevance for potential co-targeting with TROP2 and NECTIN4: Preview of Bladder BRIDGister. (ASCO-GU 2024)
Background: In view of the efficacy of FGFR targeting in early and advanced bladder cancer, as has been shown for erdafitinib in the THOR and NORSE trial, molecular testing of FGFR mutations and fusions will soon become clinical routine worldwide... PCR-based FGFR assessment by Therascreen and UroTyper is highly concordant and enables fast, local FGFR assessment within few hours. FGFR3 mutations are associated with increased TROP2 & NECTIN4 expression indicating potential synergistic options which warrants further exploration as part of molecularly stratified clinical trials.
FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor) • NECTIN4 (Nectin Cell Adhesion Molecule 4) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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FGFR3 mutation • FGFR mutation • FGFR fusion • FGFR3 S249C • FGFR3 overexpression • FGFR3 Y373C • NECTIN4 expression • FGFR3 G370C • FGFR3 R248C • FGF3 overexpression
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therascreen® FGFR RGQ RT-PCR Kit • Uromonitor®
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Balversa (erdafitinib)
4ms
Differential mutation profiles between benign and cancerous urothelium in patients with non-muscle invasive bladder cancer (NMIBC). (ASCO-GU 2024)
Analysis of the mutational profile of pBT and pNMIBC revealed differential patterns of somatic mutations. Many expected gene mutations were detected in pNMIBC, but surprisingly 18% of all mutated genes were shared between tumor and pathologically benign samples. The fact that only one somatically mutated gene was exclusive to pBT signifies excellent censoring of variants by the DeepSea algorithm.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • ARID1A (AT-rich interaction domain 1A) • KMT2A (Lysine Methyltransferase 2A) • ERCC2 (Excision repair cross-complementation group 2) • CREBBP (CREB binding protein) • NCOR1 (Nuclear Receptor Corepressor 1)
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HER-2 mutation • ARID1A mutation • FGFR3 mutation
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PredicineWES+™
4ms
Infigratinib versus placebo in patients with resected urothelial cancer (UC) bearing FGFR3 mutation or fusion: Primary DFS analysis from the phase 3, randomized PROOF302 study. (ASCO-GU 2024)
Our failure to accrue sufficient patients to the current trial precludes any definitive conclusions around the role of infigratinib as adjuvant therapy for FGFR3-altered UC. In the process of study conduct, however, we garnered substantial insights that may aid in the development of future precision oncology trials for adjuvant UC. Clinical trial information: NCT04197986.
Clinical • P3 data
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FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation • FGFR3 fusion
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Truseltiq (infigratinib)
4ms
FGFR3 mutated (FGFR3mut+) urothelial carcinoma of bladder (UCB) or upper tract (UTUC): A comparative genomic landscape study. (ASCO-GU 2024)
THOR trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs (taxane or vinflunine) in patients (pts) with advanced UCB or UTUC. Although histologically similar, the genomic landscape of FGFR3mut+ UTUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation. The findings may impact of clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents.
Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • MTAP (Methylthioadenosine Phosphorylase) • TSC1 (TSC complex subunit 1) • FUS (FUS RNA Binding Protein)
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PD-L1 expression • MSI-H/dMMR • FGFR3 mutation • FGFR3 fusion • HRD signature
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PD-L1 IHC 22C3 pharmDx
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Balversa (erdafitinib) • Javlor (vinflunine)
4ms
Non-Small Cell Lung Carcinoma with Clear Cell Features and FGFR3::TACC3 Gene Rearrangement: Clinicopathologic and Next Generation Sequencing Study of 7 Cases. (PubMed, Am J Surg Pathol)
Non-small cell lung carcinoma harboring FGFR3::TACC3 gene rearrangements is extremely rare, and this rearrangement may potentially be enriched in tumors that demonstrate clear cell histology. Identification of FGFR3::TACC3 in patients with lung carcinomas with clear cell features may be of importance as they could potentially be candidates for therapy with tyrosine kinase inhibitors.
Journal • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)
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TP53 mutation • KRAS mutation • EGFR mutation • KRAS G12D • FGFR3 mutation • KRAS G12 • EGFR mutation + KRAS mutation • FGFR3 amplification
4ms
BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)
P1, N=156, Active, not recruiting, AstraZeneca | Phase classification: P1b --> P1 | Trial completion date: Sep 2023 --> Jun 2024
Phase classification • Trial completion date
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HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • FGFR (Fibroblast Growth Factor Receptor) • CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
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PD-L1 expression • FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification
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Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)
4ms
Reactivation of telomerase reverse transcriptase expression in cancer: the role of TERT promoter mutations. (PubMed, Front Cell Dev Biol)
TERT promoter mutations have been recognized as an early marker of tumour development or a major indicator of poor outcome and reduced patients survival in several cancer types. In this review, we summarize recent findings on the role of TERT promoter mutations, telomerase expression and telomeres elongation in cancer development, their clinical significance and therapeutic opportunities.
Review • Journal
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BRAF (B-raf proto-oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • TERT (Telomerase Reverse Transcriptase) • TPP1 (Tripeptidyl Peptidase 1)
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BRAF mutation • FGFR3 mutation • TERT mutation • TERT promoter mutation
4ms
Clinical and genomic landscape of FGFR3-altered urothelial carcinoma and treatment outcomes with erdafitinib: a real-world experience. (PubMed, Clin Cancer Res)
FGFR3 mutations are common in urothelial carcinoma, whereas FGFR2 alterations are rare. Discordance of FGFR3 mutational status between primary and metastatic tumors occurs frequently and raises concern over sequencing archival primary tumors to guide patient selection for erdafitinib therapy. Erdafitinib responses were typically brief and dosing was limited by toxicity. FGFR3, AKT1, and TP53 mutations detected in cfDNA represent putative mechanisms of acquired erdafitinib resistance.
Journal • Real-world evidence • Real-world
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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TP53 mutation • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • AKT1 mutation • FGFR3 fusion
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Balversa (erdafitinib)
5ms
Pemigatinib for Metastatic or Surgically Unresectable Urothelial Carcinoma With FGF/FGFR Genomic Alterations: Final Results From FIGHT-201. (PubMed, Ann Oncol)
Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or fusions/rearrangements.
Journal • Metastases
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FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR3 mutation • FGFR3 S249C • FGFR3 fusion • FGFR3 V555M
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Pemazyre (pemigatinib)
5ms
Retrospective data • Journal • Real-world evidence • Next-generation sequencing • IO biomarker • Real-world • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3)
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PIK3CA mutation • FGFR3 mutation • FGFR3 fusion
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Herceptin (trastuzumab) • Piqray (alpelisib) • Balversa (erdafitinib)
5ms
Ipsilateral synchronous papillary renal neoplasm with reverse polarity and urothelial carcinoma in a renal transplant recipient: a rare case report with molecular analysis and literature review. (PubMed, Diagn Pathol)
We report here for the first time an extraordinarily rare case of synchronous renal tumors of a PRNRP and UC in the ipsilateral kidney of an RTR. We identified simultaneous KRAS, FGFR3, and KDM6A mutations in two different renal masses in the ipsilateral kidney. Pathologic assessment with comparative molecular analysis of mutational profiles facilitates tumor studies after RT and may be of great value in clinical management strategies.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase) • FGFR3 (Fibroblast growth factor receptor 3) • KDM6A (Lysine Demethylase 6A)
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KRAS mutation • KRAS G12D • FGFR3 mutation • FGFR3 S249C • KRAS G12 • KRAS exon 2 mutation • KDM6A mutation
5ms
COMUTATIONAL PATTERNS IN FGFR3-ALTERED NON-MUSCLE INVASIVE BLADDER CANCER INFLUENCE RECURRENCE AND PROGRESSION (SUO 2023)
As Erdafitinib, an FGFR1-4 inhibitor, has recently been approved for locally advanced and metastatic bladder cancer, numerous trials that assess the role and efficacy of FGFR inhibitors in the treatment of non-muscle-invasive disease have commenced... Trials of FGFR-inhibitors are ongoing in NMIBC. We predict that the diversity of response to these drugs in FGFR3-altered NMIBC will be dependent on co-mutational patterns, and identified three co-alterations (CDKN1A, CDKN2A, TP53) that affect the high-grade recurrence-free survival and clinical progression-free survival of patients with FGFR3-altered tumors. Future studies regarding the effect of these and other co-alterations on recurrence, progression, metastasis, and drug resistance in FGFR3-altered tumors are warranted and will provide more insight into the true efficacy of this new class of targeted therapies.
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CREBBP (CREB binding protein) • KDM6A (Lysine Demethylase 6A) • STAG2 (Stromal Antigen 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • E2F3 (E2F transcription factor 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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TP53 mutation • FGFR3 mutation • CDKN2A mutation • STAG2 mutation
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MSK-IMPACT
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Balversa (erdafitinib)
5ms
DETECTION, RISK STRATIFICATION, AND THERAPUETIC SELECTION FOR UPPER TRACT UROTHELIAL CARCINOMA WITH URINE-BASED COMPREHENSIVE GENOMIC PROFILING (SUO 2023)
uCGP provides clinicians with diagnostic and prognostic insights into their patient's disease. This is of particular importance in UTUC where lesions are often small and difficult to detect, stage, and thus treat. uCGP can be used to appropriately risk stratify patients and can identify patients who may benefit from first line systemic therapy, versus immediate surgery, based on FGFR3 and MSI/TMB status.
Tumor mutational burden
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation • FGFR3 positive
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UroAmp
5ms
Alanine restriction can inhibit carcinogenesis in a novel mouse model of upper tract urothelial carcinoma (SUO 2023)
Firstly, we have established a novel mouse model developing UTUC that genetically mimics human UTUC. Secondly, alanine restriction can suppress UTUC carcinogenesis in this model.
Preclinical
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FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation
5ms
Examining Rare Genitourinary Cancers for Genetic Biomarkers to Explore Potential Targeted Therapy Options (AMP 2023)
Data from this small cohort of rare tumors suggest that SCNC and SqCB exhibit common driver/targetable mutations seen in other hematologic and solid tumors that might represent new therapeutic targets in these rare tumor types. Our identification of mutations unique to different histologies in the same tumor argues for independent sequencing of different histologies to broaden the search for targetable mutations.
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CCND1 (Cyclin D1)
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TP53 mutation • PIK3CA mutation • NF1 mutation • FGFR3 mutation • CDKN2A mutation • CCND1 amplification • FGFR3 fusion • TERT mutation • TERT promoter mutation
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TruSight Tumor 170 Assay
6ms
Enrollment open
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BGLAP (Bone Gamma-Carboxyglutamate Protein)
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FGFR3 mutation
6ms
Mutational landscape and characteristics of ERBB2 in urothelial carcinoma (ESMO Asia 2023)
Conclusions The study provided the landscape of ERBB2 alterations in UC that may benefit from anti-HER2 agents. Consideration should be given to developing trials inclusive of patients with UC harboring ERBB2 alterations.
Tumor mutational burden
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ERCC2 (Excision repair cross-complementation group 2) • KMT2C (Lysine Methyltransferase 2C)
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TP53 mutation • TMB-H • HER-2 amplification • HER-2 mutation • HER-2 L755S • NF1 mutation • FGFR3 mutation • HER-2 S310F • ERBB3 mutation
6ms
Analysis of several common APOBEC-type mutations in bladder tumors suggests links to viral infection. (PubMed, Cancer Prev Res (Phila))
BKPyV tumor positivity in the NMIBC subset with FGFR3- or PIK3CA-mutated tumors was also associated with a higher risk of progression to MIBC (p=0.019). In conclusion, our results support smoking and BKPyV infection as risk factors contributing to bladder tumorigenesis in the general patient population through distinct molecular mechanisms.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3)
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PIK3CA mutation • PIK3CA E545K • FGFR3 mutation • FGFR3 S249C • PIK3CA E542K • PIK3CA E545 • PIK3CA E542 • FGFR3 Y375C
6ms
Fibroblast growth factor receptor 3 mutation attenuates response to immune checkpoint blockade in metastatic urothelial carcinoma by driving immunosuppressive microenvironment. (PubMed, J Immunother Cancer)
FGFR3 mutation can attenuate prognosis and response to ICB in patients with metastatic UC. FGFR3-mutated UC carries a stronger immunosuppressive microenvironment in comparison with FGFR3-wildtype UC. Inhibition of FGFR3 might activate the immune microenvironment, and the combination of FGFR inhibitor targeted therapy and ICB might be a promising therapeutic regimen in metastatic UC, providing important implications for UC clinical management.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • Checkpoint block • Metastases
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FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation • FGFR wild-type
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Tecentriq (atezolizumab)
6ms
Phase 3 THOR study: Results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt) (DGHO 2023)
Pts (≥18 y) with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), ECOG performance status 0-2, adequate organ function, progression on/after prior systemic therapy (tx) that included an anti-PD-(L)1 agent, and ≤2 prior lines of tx were randomized 1:1 to receive erda (8 mg with pharmacodynamically guided uptitration to 9 mg on day 14) QD or investigator’s choice of chemo (docetaxel or vinflunine) Q3W until disease progression or intolerable toxicity. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
Clinical • P3 data • Metastases
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FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR3 mutation • FGFR3 fusion
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docetaxel • Balversa (erdafitinib) • Javlor (vinflunine)
6ms
FGFR3 alterations in bladder cancer stimulate serine synthesis to induce immune-inert macrophages that suppress T-cell recruitment and activation. (PubMed, Cancer Res)
Targeting PI3K in aFGFR3 tumors with duvelisib achieved promising efficacy by reversing the macrophage phenotype, and combination therapy with duvelisib and erdafitinib demonstrated increased antitumor activity. Overall, these findings reveal the critical role of enhanced serine synthesis efflux from cancer cells with mutant FGFR3 in shifting macrophages to an immune-inert phenotype. Reversing the macrophage phenotype holds promise for enhancing erdafitinib efficacy.
Journal
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FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation
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Balversa (erdafitinib) • Copiktra (duvelisib)
6ms
Nested and Large Nested Subtypes of Urothelial Carcinoma of the Upper Urinary Tract: A Multi-Institutional Study. (PubMed, Mod Pathol)
FGFR3 mutations were also more common in low stage tumors. This study expands on the clinicopathological spectrum of NUC and LNUC of the upper urinary tract and is the first to comprehensively analyze the molecular profile of these tumors, highlighting pathogenic genetic alterations of potential therapeutic and prognostic value.
Journal • Clinical • Tumor mutational burden
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR3 (Fibroblast growth factor receptor 3)
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PIK3CA mutation • FGFR3 mutation
|
Idylla™ MSI Test
7ms
Genomic profiling of high-risk smoldering myeloma patients treated with a curative strategy: a biological study of the phase II GEM CESAR clinical trial. (IMW 2023)
The mutational profile of HR SMM patients is similar to symptomatic MM. If validated in larger studies, t(4; 14) plus FGFR3 mutations, or NRAS mutations, could be used to predict resistance and a shorter time to disease progression.
Clinical • P2 data
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • SDC1 (Syndecan 1) • TENT5C (Terminal Nucleotidyltransferase 5C)
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NRAS mutation • FGFR3 mutation • NRAS G13
7ms
A Study of Oral Erdafitinib in People With Recurrent Non-Invasive Bladder Cancer (clinicaltrials.gov)
P2; Trial completion date: Aug 2023 --> Aug 2025 | Trial primary completion date: Aug 2023 --> Aug 2025
Trial completion date • Trial primary completion date
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FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 G370C • FGFR3 R248C
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MSK-IMPACT
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Balversa (erdafitinib)
8ms
Inhibition of FGFR3 upregulates MHC-I and PD-L1 via TLR3/NF-kB pathway in muscle-invasive bladder cancer. (PubMed, Cancer Med)
Together, our results suggest that FGFR3 might involve in immunosuppression by inhibition of NF-kB pathway in BC. Considering that TLR3 agonists are currently approved for clinical treatment as immunoadjuvants, our study might provide more insights for improving the efficacy of immunotherapy in MIBC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • TLR3 (Toll Like Receptor 3)
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PD-L1 expression • FGFR3 mutation
8ms
RNA-seq profiling of upper tract urothelial carcinoma: bladder cancer consensus classification relevance, molecular heterogeneity and differential immune signatures. (PubMed, Mod Pathol)
Most LumP tumors showed low immune infiltration and PD-L1 expression and high proportion of FGFR3 mutations. These findings suggest differential response to novel therapies between UTUC and MIBC patients.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • GATA3 (GATA binding protein 3)
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PD-L1 expression • PD-L1 overexpression • MSI-H/dMMR • FGFR3 mutation • FGFR3 expression
8ms
Urinary tumor DNA MRD analysis to identify responders to neoadjuvant immunotherapy in muscle-invasive bladder cancer. (PubMed, Clin Cancer Res)
These findings demonstrate the safety and efficacy of neoadjuvant toripalimab, and suggest the immense potential of noninvasive utDNA MRD testing to guide tailored decision-making with regard to bladder preservation and change the current treatment paradigm for MIBC patients.
Journal • PD(L)-1 Biomarker • IO biomarker
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FGFR3 (Fibroblast growth factor receptor 3)
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FGFR3 mutation
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Loqtorzi (toripalimab-tpzi)
8ms
Feasibility of ex vivo drug sensitivity testing in urothelial cancer: EVITA trial (ESMO 2023)
For ex vivo drug testing, tumor clusters were isolated, seeded, and exposed to single-agent chemotherapy: carboplatin, cisplatin, gemcitabine and targeted therapy (erdafitinib). A correlation with clinical response to chemotherapy could not be established due to a lack of successfully screened patients with matching clinical chemotherapy treatment. For NMIBC, however, differential ex vivo sensitivity to gemcitabine, and a preliminary correlation for ex vivo erdafitinib sensitivity and FGFR3 mutation status offers a potential solution to select NMIBC patients for effective (novel) treatment options.
Preclinical
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • TERT (Telomerase Reverse Transcriptase)
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PIK3CA mutation • FGFR3 mutation • TERT mutation • FGFR3 Y375C • FGFR wild-type
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cisplatin • carboplatin • gemcitabine • Balversa (erdafitinib)