ArticleCancer discovery2013
Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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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.
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Who cites it
71 citing papers in PubMed, 129 citations in OpenAlex.
- FGFR3 oncogenic activation drives oxidative metabolic reprogramming in bladder cancer: a systems metabolomics approach.Communications biology · 2026Article
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- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies.Cancer communications (London, England) · 2024Review
- The roles of FGFR3 and c-MYC in urothelial bladder cancer.Discover oncology · 2024Review
- A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants.Cancer research · 2024Article
- Targeting FGFR for cancer therapy.Journal of hematology & oncology · 2024Review
- TGFβ overcomes FGF-induced transinhibition of EGFR in lens cells to enable fibrotic secondary cataract.Molecular biology of the cell · 2024Article
- FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.Nature reviews. Clinical oncology · 2024Review
- Adipocyte Precursor-Derived NRG1 Promotes Resistance to FGFR Inhibition in Urothelial Carcinoma.Cancer research · 2024Article
- Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcome.Molecular cancer · 2024Article
- Resistance to Selective FGFR Inhibitors in FGFR-Driven Urothelial Cancer.Cancer discovery · 2023Article
- Article
- RNA-seq reveals novel mechanistic targets of Livin in bladder cancer.BMC urology · 2023Article
- Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro.The Journal of pathology · 2023Article
- Targeting the FGF/FGFR axis and its co-alteration allies.ESMO open · 2022Article
- Dual targeting of FGFR3 and ERBB3 enhances the efficacy of FGFR inhibitors in FGFR3 fusion-driven bladder cancer.BMC cancer · 2022Article
- EGFR Inhibition Potentiates FGFR Inhibitor Therapy and Overcomes Resistance in FGFR2 Fusion-Positive Cholangiocarcinoma.Cancer discovery · 2022Article
- Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.Cancers · 2022Review
- Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors HarboringCancer discovery · 2022Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledActivation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies. SIGNIFICANCE: Our data identify a novel therapeutic approach to the treatment of FGFR3-mutant cancer, emphasizing the potential of combination approaches targeting both FGFR3 and EGFR. Our data extend the role of EGFR in mediating resistance to inhibitors targeting a mutant oncogene, showing that EGFR signaling can repress mutant FGFR3 to induce intrinsic resistance to FGFR targeting.
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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.