# Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer

Source: https://onco.cc/key-papers/paper-weiss-fgfr1-amplification-squamous-lung-sci-transl-med-2010/  
OnCo record `paper-weiss-fgfr1-amplification-squamous-lung-sci-transl-med-2010` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A search for anything treatable in squamous lung cancer found extra copies of one growth-factor receptor gene in about a fifth of cases, and cells carrying those extra copies died when the receptor was blocked.

## Summary

A systematic search across 232 lung cancer specimens for therapeutically amenable genetic alterations, followed by high-resolution copy-number analysis, identified frequent and focal FGFR1 amplification in squamous cell lung cancer (155 cases) but not in other lung cancer subtypes, and fluorescence in situ hybridisation confirmed amplification in 22% of an independent squamous cohort. Screening 83 lung cancer cell lines with the FGFR inhibitor PD173074 showed growth inhibition and apoptosis specifically in FGFR1-amplified cells. Dependence was validated by FGFR1 knockdown and by rescuing amplified cells with an inhibitor-resistant FGFR1 allele, and FGFR1 inhibition produced significant tumour shrinkage in vivo.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Science Translational Medicine
- Year: 2010
- DOI: 10.1126/scitranslmed.3001451
- Authors: Weiss J, Sos ML, Seidel D, et al.
- Findings: Focal FGFR1 amplification in squamous lung cancer and not in other subtypes, confirmed in 22% of an independent cohort.; Amplified cell lines are selectively killed by FGFR inhibition.; Dependence confirmed by knockdown and by an inhibitor-resistant allele.; Tumour shrinkage in vivo.
- What it means: It was the first therapeutically tractable alteration found in squamous lung cancer, and in the decade since it has become the standard example of amplification not equalling dependence, because copy number alone has selected patients poorly in trials.
- Caveats: Preclinical dependence does not predict clinical response, and FGFR inhibitor trials selected on copy number have had low response rates.; Amplification calls vary with platform and threshold.; Messenger RNA expression, not measured here, separates dependent from non-dependent amplified tumours better than copy number does.

## Sources

- Weiss et al., Sci Transl Med 2010: frequent and focal FGFR1 amplification in squamous cell lung cancer: https://doi.org/10.1126/scitranslmed.3001451
- PubMed: https://pubmed.ncbi.nlm.nih.gov/21160078/

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [FGFR1](https://onco.cc/targets/fgfr1/)
- pathways: [FGF / FGFR signalling](https://onco.cc/pathways/fgfr-signalling/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Amplification](https://onco.cc/terms/amplification/), [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Gene amplification and copy-number change](https://onco.cc/terms/gene-amplification/)
- people: [Roman Thomas](https://onco.cc/people/roman-thomas/)
- journals: [Science Translational Medicine](https://onco.cc/journals/science-translational-medicine/)

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