Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a Pan-FGFR inhibitor in a mouse model of NSCLC.
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Abstract | Somatic mutations in FGFR2 are present in 4% to 5% of patients diagnosed with non-small cell lung cancer (NSCLC). Amplification and mutations in FGFR genes have been identified in patients with NSCLCs, and clinical trials are testing the efficacy of anti-FGFR therapies. FGFR2 and other FGFR kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma, although mouse models of FGFR-driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade 3/4 adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting. |
Year of Publication | 2014
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Journal | Cancer Res
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Volume | 74
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Issue | 17
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Pages | 4676-84
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Date Published | 2014 Sep 01
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ISSN | 1538-7445
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URL | |
DOI | 10.1158/0008-5472.CAN-13-3218
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PubMed ID | 25035393
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PubMed Central ID | PMC4154986
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Grant list | P50CA090578 / CA / NCI NIH HHS / United States
CA166480 / CA / NCI NIH HHS / United States
R01 CA122794 / CA / NCI NIH HHS / United States
K08 CA163677 / CA / NCI NIH HHS / United States
1K08CA163677 / CA / NCI NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
CA163896 / CA / NCI NIH HHS / United States
P01 CA154303 / CA / NCI NIH HHS / United States
R01 CA163896 / CA / NCI NIH HHS / United States
R01 CA166480 / CA / NCI NIH HHS / United States
CA122794 / CA / NCI NIH HHS / United States
R01 CA140594 / CA / NCI NIH HHS / United States
CA140594 / CA / NCI NIH HHS / United States
CA120964 / CA / NCI NIH HHS / United States
P50 CA090578 / CA / NCI NIH HHS / United States
CA154303 / CA / NCI NIH HHS / United States
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