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Editorial
. 2023 Nov 1;133(21):e174171.
doi: 10.1172/JCI174171.

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

Netta Mäkinen  1   2 , Matthew Meyerson  1   2   3
Affiliations
Editorial

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

Netta Mäkinen et al. J Clin Invest. .

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.

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Conflict of interest statement

Conflict of interest: MM receives research support from Bayer, Ono, and Janssen; patent licensing royalties from Bayer (patents including US patent no. 11,427,553, “Dihydrooxadiazinones”; US patent no. 11,339,157, “4H-pyrrolo[3,2-c]pyridin-4-one derivatives”; US patent no. 11,207,320, “Compositions and methods for cancer expressing PDE3A or SLFN12”; US patent no. 11,142,522, “Compounds, compositions and methods for cancer treatment”; US patent no. 10,966,986, “Compounds, compositions and methods for cancer patient stratification and cancer treatment”; and US patent no. 9,890,127, “Compounds and compositions for the treatment of cancer,” as well as patents pending) and LabCorp (US patent nos. 10,669,589; 10,000,815; 9,035,036; 8,465,916; 8,105,769; 7,964,349; and 7,294,468; all titled “Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments,” as well as patents pending); and serves as a scientific advisory board member and consultant with ownership interest in and income for Delve Bio, Interline, and Isabl.

Figures

Figure 1
Figure 1. Two types of FGFR1 rearrangements are associated with sensitivity to FGFR inhibition in LSCC.
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.
See this image and copyright information in PMC

Comment on

  • Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer.
    Malchers F, Nogova L, van Attekum MH, Maas L, Brägelmann J, Bartenhagen C, Girard L, Bosco G, Dahmen I, Michels S, Weeden CE, Scheel AH, Meder L, Golfmann K, Schuldt P, Siemanowski J, Rehker J, Merkelbach-Bruse S, Menon R, Gautschi O, Heuckmann JM, Brambilla E, Asselin-Labat ML, Persigehl T, Minna JD, Walczak H, Ullrich RT, Fischer M, Reinhardt HC, Wolf J, Büttner R, Peifer M, George J, Thomas RK. Malchers F, et al. J Clin Invest. 2023 Nov 1;133(21):e170217. doi: 10.1172/JCI170217. J Clin Invest. 2023. PMID: 37606995 Free PMC article.

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