ArticleCancer discovery2016
High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 1 of them a synthesis that pooled it.
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.
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
157 citing papers in PubMed, 1 synthesis or guideline pooled it, 273 citations in OpenAlex.
- Pooled it
- Phase II Study of Erdafitinib in Patients With Tumors WithJCO precision oncology · 2024Trial
- A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial.Cancer research and treatment · 2024Trial
- Trial
- Trial
- Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- TBCRC 032 IB/II Multicenter Study: Molecular Insights to AR Antagonist and PI3K Inhibitor Efficacy in Patients with ARClinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Trial
- Review
- FGFR1 Promotes Malignant Progression in Lung Squamous Cell Carcinoma Through Activation of Wnt/β-Catenin Signaling.Cancer medicine · 2026Article
- Article
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- Review
- PI3Kα Inhibitor and Degrader Inavolisib Can Co-opt FGFR2 to Enhance Responses in Patients with PIK3CA-Mutated Solid Tumors and in Preclinical Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Identification of small molecule inhibitors targeting FGFR through molecular docking-based screening.Frontiers in oncology · 2026Article
- Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer.Frontiers in oncology · 2026Review
- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- The Role of FGFR2 as a Novel Biomarker for Treatment of Gastric Cancer-A Literature Review.Medicina (Kaunas, Lithuania) · 2025Review
- Phase Ib Trial of Fulvestrant, Palbociclib, and Erdafitinib, a pan-FGFR Tyrosine Kinase Inhibitor, in HR+/HER2- Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Clinical Significance of Extrachromosomal DNA inJCO precision oncology · 2025Article
97 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
27 authors at 8 institutions in 2 countries.
Funding
Abstract
unlabelledFGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1-amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy. SIGNIFICANCE: Robust single-agent response to FGFR inhibition is seen only in high-level FGFR-amplified cancers, with copy-number level dictating response to FGFR inhibition in vitro, in vivo, and in the clinic. High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients. Cancer Discov; 6(8); 838-51. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803.
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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.