ArticleCancer discovery2023
Resistance to Selective FGFR Inhibitors in FGFR-Driven Urothelial Cancer.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 67 citations in OpenAlex.
- Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial.Signal transduction and targeted therapy · 2024Trial
- Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development.Molecular cancer · 2024Trial
- Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial.Nature medicine · 2024Trial
- FGFR3-driven gene regulatory network analysis reveals a protumoral role for p63 in luminal bladder tumors.The Journal of clinical investigation · 2026Article
- Response to letter to the editor for "Infigratinib low dose therapy is an effective strategy to treat hypochondroplasia".Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Dynamic Precision Oncology for Real-Time Molecular Monitoring and Management in Urothelial Carcinoma.International journal of molecular sciences · 2026Review
- Dabogratinib (TYRA-300), an FGFR3 Isoform-Selective Inhibitor: Preclinical and Initial Clinical Evidence of Antitumor Activity.Molecular cancer therapeutics · 2026Article
- Prospective multicenter study of ctDNA versus tumor tissue guiding FGFR-targeted therapy in metastatic urothelial cancer.Nature communications · 2026Article
- Targeted therapies for urothelial carcinoma: From FGFR inhibitors to next‑generation antibody-drug conjugates (Review).International journal of oncology · 2026Review
- Integrated Genomic and Single-Cell Analysis Reveals Heterogeneity, Prognosis, and Treatment Vulnerability in Urothelial Carcinoma.Human mutation · 2026Article
- Saturation mutagenesis identifies activating and resistance-inducing FGFR kinase domain mutations.Nature genetics · 2026Article
- Treating T24 cells with erianin restores gefitinib drug sensitivity by regulating MYLK to inhibit EGFR and EMT processes.American journal of cancer research · 2026Article
- The international and domestic research trends of targeted therapy in bladder cancer: a bibliometric analysis of the past three decades.Frontiers in oncology · 2026Review
- Design and synthesis of an erdafitinib-based selective FGFR2 degrader.Beilstein journal of organic chemistry · 2026Article
- Article
- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies.Nature reviews. Urology · 2025Review
- MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells.Cell death & disease · 2025Article
- Erdafitinib suppresses pathological retinal angiogenesis via dual targeting of FGFR and VEGFR2 signaling.Scientific reports · 2025Article
- Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients.Scientific reports · 2025Article
Corrections and comments
- Commented on by
Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Several fibroblast growth factor receptor (FGFR) inhibitors are approved or in clinical development for the treatment of FGFR-driven urothelial cancer, and molecular mechanisms of resistance leading to patient relapses have not been fully explored. We identified 21 patients with FGFR-driven urothelial cancer treated with selective FGFR inhibitors and analyzed postprogression tissue and/or circulating tumor DNA (ctDNA). We detected single mutations in the FGFR tyrosine kinase domain in seven (33%) patients (FGFR3 N540K, V553L/M, V555L/M, E587Q; FGFR2 L551F) and multiple mutations in one (5%) case (FGFR3 N540K, V555L, and L608V). Using Ba/F3 cells, we defined their spectrum of resistance/sensitivity to multiple selective FGFR inhibitors. Eleven (52%) patients harbored alterations in the PI3K-mTOR pathway (n = 4 TSC1/2, n = 4 PIK3CA, n = 1 TSC1 and PIK3CA, n = 1 NF2, n = 1 PTEN). In patient-derived models, erdafitinib was synergistic with pictilisib in the presence of PIK3CA E545K, whereas erdafitinib-gefitinib combination was able to overcome bypass resistance mediated by EGFR activation. SIGNIFICANCE: In the largest study on the topic thus far, we detected a high frequency of FGFR kinase domain mutations responsible for resistance to FGFR inhibitors in urothelial cancer. Off-target resistance mechanisms involved primarily the PI3K-mTOR pathway. Our findings provide preclinical evidence sustaining combinatorial treatment strategies to overcome bypass resistance. See related commentary by Tripathi et al., p. 1964. This article is featured in Selected Articles from This Issue, p. 1949.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.