Genomic insights into the mechanisms of FGFR1 dependency in squamous cell lung cancer
Netta Mäkinen, Matthew Meyerson
Netta Mäkinen, Matthew Meyerson
Published November 1, 2023
Citation Information: J Clin Invest. 2023;133(21):e174171. https://doi.org/10.1172/JCI174171.
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Commentary

Genomic insights into the mechanisms of FGFR1 dependency in squamous cell lung cancer

Abstract

Although subsets of patients with lung squamous cell carcinoma (LSCC) benefit from immunotherapy, there are few effective molecularly targeted treatments for LSCC. Fibroblast growth factor receptor (FGFR) inhibitors provide a therapeutic option for patients with LSCC harboring FGFR aberrations, but their therapeutic efficacy has been limited to date. In this issue of the JCI, Malchers et al. identified tail-to-tail rearrangements, either within or near FGFR1, that are associated with FGFR1 dependency and sensitivity to FGFR inhibition in LSCC. These results may help improve the selection of patients with LSCC who are most likely to benefit from treatment with FGFR inhibitors.

Authors

Netta Mäkinen, Matthew Meyerson

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Figure 1

Two types of FGFR1 rearrangements are associated with sensitivity to FGFR inhibition in LSCC.

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Two types of FGFR1 rearrangements are associated with sensitivity to FGF...
Only a subset of patients with LSCC characterized by amplification of the 8p11-12 region, which houses the putative FGFR1 oncogene, respond to FGFR inhibition. Malchers et al. showed that LSCC tumors with intragenic tail-to-tail rearrangements within FGFR1 and in close proximity to FGFR1 were associated with FGFR1 dependency (24). Screening patients for these rearrangement events may identify those more likely to benefit from treatment with FGFR inhibitors.