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Cancer Res DOI:10.1158/0008-5472.CAN-13-3218

Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a Pan-FGFR inhibitor in a mouse model of NSCLC.

Publication TypeJournal Article
Year of Publication2014
AuthorsTchaicha, JH, Akbay, EA, Altabef, A, Mikse, OR, Kikuchi, E, Rhee, K, Liao, RG, Bronson, RT, Sholl, LM, Meyerson, M, Hammerman, PS, Wong, K-K
JournalCancer Res
Volume74
Issue17
Pages4676-84
Date Published2014 Sep 01
ISSN1538-7445
KeywordsAdenocarcinoma, Animals, Animals, Genetically Modified, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Disease Models, Animal, Female, Humans, Lung Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mutation, Protein Kinase Inhibitors, Receptor, Fibroblast Growth Factor, Type 2, Tumor Suppressor Protein p53
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.

URLhttp://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25035393
DOI10.1158/0008-5472.CAN-13-3218
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25035393?dopt=Abstract

Alternate JournalCancer Res.
PubMed ID25035393
PubMed Central IDPMC4154986
Grant ListP50CA090578 / 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