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Updated: Apr 15, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
FGFR1 amplifications in squamous cell carcinomas of the lung: diagnostic and therapeutic implications
Hans-Ulrich Schildhaus1, Lucia Nogova2, Jürgen Wolf2
1Institute of Pathology, University Hospital Cologne, Cologne, Germany ; ; Center for Integrated Oncology Cologne/Bonn, Germany ;
Abstract:
Fibroblast growth factor receptor 1 (FGFR1) is a type 4 receptor tyrosine kinase. The receptor and its ligands play an important role in development and physiology. However, constitutive activation of FGFR1 by gene amplification, translocation or mutation is associated with various malignancies as, for example, breast cancer or myeloproliferative diseases. We have recently reported that FGFR1 amplification occurs in 20% of pulmonary squamous cell carcinomas, and preclinical tests have shown that these alterations are therapeutically tractable. These findings make FGFR1 amplification a potential biomarker for lung cancer treatment. Squamous cell carcinomas of the lung are characterized by an uneven FGFR1 gene copy number distribution. Therefore, fluorescence in situ hybridization assays need to address focality and heterogeneity of FGFR1 in these tumors. Here, we review our proposal for a reading and evaluation strategy. Furthermore, we highlight the emerging landscape of clinical trials with selective and unselective FGFR inhibitors and provide first response data from early clinical trials.
Insights
Fibroblast growth factor receptor 1 (FGFR1) amplification is found in 20% of lung squamous cell carcinomas and is a targetable alteration. This FGFR1 biomarker shows promise for guiding lung cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Fibroblast growth factor receptor 1 (FGFR1) is a receptor tyrosine kinase crucial for development and physiology.
- Aberrant FGFR1 activation through gene amplification, translocation, or mutation is linked to various cancers, including breast cancer and myeloproliferative diseases.
Purpose of the Study:
- To investigate the prevalence and therapeutic tractability of FGFR1 amplification in pulmonary squamous cell carcinomas.
- To propose a reading and evaluation strategy for fluorescence in situ hybridization (FISH) assays assessing FGFR1 heterogeneity in lung tumors.
- To review the current landscape of clinical trials involving FGFR inhibitors and present early response data.
Main Methods:
- Analysis of FGFR1 gene copy number in pulmonary squamous cell carcinomas.
- Development and proposal of a FISH assay reading and evaluation strategy.
- Review of ongoing clinical trials and early response data for FGFR inhibitors.
Main Results:
- FGFR1 amplification was identified in 20% of pulmonary squamous cell carcinomas.
- Preclinical data indicate that FGFR1 alterations are therapeutically tractable.
- Lung squamous cell carcinomas exhibit heterogeneous FGFR1 gene copy number distribution.
Conclusions:
- FGFR1 amplification represents a potential predictive biomarker for lung cancer treatment.
- A standardized FISH assay strategy is necessary to address the focality and heterogeneity of FGFR1 in these tumors.
- Emerging FGFR inhibitors show promise, with early clinical trial data indicating therapeutic potential.
