Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Tchaicha, JH, Akbay, EA, Altabef, A, Mikse, OR, Kikuchi, E, Rhee, K, Liao, RG, Bronson, RT, Sholl, LM, Meyerson, M, Hammerman, PS, Wong, K-K |
Journal | Cancer Res |
Volume | 74 |
Issue | 17 |
Pages | 4676-84 |
Date Published | 2014 Sep 01 |
ISSN | 1538-7445 |
Keywords | Adenocarcinoma, 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. |
URL | http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25035393 |
DOI | 10.1158/0008-5472.CAN-13-3218 |
Pubmed | |
Alternate Journal | Cancer Res. |
PubMed ID | 25035393 |
PubMed Central ID | PMC4154986 |
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 |
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.
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