論文

査読有り 国際誌
2014年9月1日

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

Cancer research
  • Jeremy H Tchaicha
  • ,
  • Esra A Akbay
  • ,
  • Abigail Altabef
  • ,
  • Oliver R Mikse
  • ,
  • Eiki Kikuchi
  • ,
  • Kevin Rhee
  • ,
  • Rachel G Liao
  • ,
  • Roderick T Bronson
  • ,
  • Lynette M Sholl
  • ,
  • Matthew Meyerson
  • ,
  • Peter S Hammerman
  • ,
  • Kwok-Kin Wong

74
17
開始ページ
4676
終了ページ
84
記述言語
英語
掲載種別
DOI
10.1158/0008-5472.CAN-13-3218

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.

リンク情報
DOI
https://doi.org/10.1158/0008-5472.CAN-13-3218
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25035393
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154986

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