2011 Fiscal Year Final Research Report
Development of individual therapy for overcoming HGF-induced molecular targeted drug-resistance in EGFR-mutant lung cancer
| Project/Area Number |
21390256
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
YANO Seiji 金沢大学, がん進展制御研究所, 教授 (30294672)
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| Co-Investigator(Kenkyū-buntansha) |
WANG Wei 金沢大学, がん研究所, 博士研究員 (80467117)
YAMADA Tadaaki 金沢大学, 附属病院, 助教 (00507048)
TAKEUCHI Shinji 金沢大学, がん進展制御研究所, 助教 (90565384)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 肺癌 / EGFR-TKI / 薬剤耐性 / HGF / Met / EGFR遺伝子変異 / バイオマーカー |
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| Research Abstract |
The purpose of this study was to develop novel therapy for overcoming HGF-induced EGFR-TKI resistance and establish biomarkers which predict the HGF-induced resistance in lung cancer. We found that inhibitors of HGF-Met could overcome HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer cells in vitro and in vivo. Our study with clinical specimens reveled that high levels of HGF were detected in tumors with acquired and intrinsic resistance to EGFR-TKI and was the most prevalent factor for resistance, at least in Japanese patients with EGFR-mutant lung cancer. We further demonstrated that levels of HGF in plasma before EGFR-TKI treatment inversely correlated with clinical response in lung cancer. These finding suggest that HGF is the important target and biomarker of individual therapy with EGFR-TKI in lung cancer.
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Research Products
(27 results)
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[Journal Article] E7050, a Met kinase inhibitor, reverses three different mechanisms of hepatocyte growth factor-induced resistance to tyrosine kinase inhibitors in EGFR mutant lung cancer cells2012
Author(s)
Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Uenaka T, Yano S
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Journal Title
Clin Cancer Res
Volume: 18
Pages: 1663-71
DOI
Peer Reviewed
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[Journal Article] Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort2011
Author(s)
Yano S, Yamada T, Takeuchi S, Tachibana K, Minami Y, Yatabe Y, Mitsudomi T, Tanaka H, Kimura T, Kudoh S, Nokihara H, Ohe Y, Yokota J, Uramoto U, Yasumoto Y, Kiura K, Higashiyama M, Oda M, Saito H, Yoshida J, Kondoh K, Noguchi M.
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Journal Title
J Thorac Oncol
Volume: 6
Pages: 2011-7
DOI
Peer Reviewed
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[Journal Article] The EGFR ligands amphiregulin and heparin-binding EGF-like growth factor promote peritoneal carcinomatosis in CXCR4-expressing gastric cancer2011
Author(s)
Yasumoto K, Yamada T, Kawashima A, Wang W, Li Q, Donev IS, Takeuchi S, Mouri H, Yamashita K, Ohtsubo K, Yano S.
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Journal Title
Clin Cancer Res
Volume: 17
Pages: 3619-30
DOI
Peer Reviewed
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[Journal Article] E7080 suppresses hematogenous multiple organ metastases of lung cancer cells with nonmutated epidermal growth factor receptor2011
Author(s)
Ogino H, Hanibuchi M, Kakiuchi S, Trung Van The, Goto H, Ikuta K, Yamada T, Uehara H, Tsuruoka A, Uenaka T, Wang W, Li Q, Takeuchi S, Yano S, Nishioka Y, Sone S.
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Journal Title
Mol Cancer Ther
Volume: 10
Pages: 1218-28
DOI
Peer Reviewed
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[Journal Article] Pleural mesothelioma instigates tumor associated fibroblasts to promote prog-ression via malignant cytokine network2011
Author(s)
Li Q, Wang W, Yamada T, Matsumoto K, Bando Y, Uehara H, Nishioka Y, Sone S, Iwakiri S, Itoi K, Utsugi T, Yano S.
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Journal Title
Am J Pathol
Volume: 179
Pages: 1483-93
DOI
Peer Reviewed
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[Journal Article] Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice2010
Author(s)
Sakaguchi S, Goto H, Hanibuchi M, Otsuka S, Ogino H, Kakiuchi S, Uehara H, Yano S, Nishioka Y, Sone S
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Journal Title
Clin Exp Metastasis
Volume: 27
Pages: 351-9
DOI
Peer Reviewed
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[Journal Article] Crosstalk to stromal fibroblasts induces resistance of lung cancer to EGFR tyrosine kinase inhibitors2009
Author(s)
Wang W, Li Q, Yamada T, Matsumoto K, Matsumoto I, Oda M, Watanabe G, Kayano Y, Nishioka Y, Sone S, Yano S
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Journal Title
Clin Cancer Res
Volume: 15
Pages: 6630-8
DOI
Peer Reviewed
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[Journal Article] E7080, a multi-tyrosine kinase inhibitor, suppresses the progression of malignant pleural mesothelioma with different proangio-genic cytokine production profiles2009
Author(s)
Ikuta K, Yano S, Trung TV, Hanibuchi M, Goto H, Li Q, Wang W, Yamada T, Ogino H, Kakiuchi S, Uehara H, Sekido Y, Uenaka T, Nishioka Y, Sone S
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Journal Title
Clin Cancer Res
Volume: 15
Pages: 7229-37
DOI
Peer Reviewed
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[Presentation] Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort. 2011 American Society of Clinical Oncology(ASCO)2011
Author(s)
Yano S, Yamada T, Takeuchi S, Tachibana K, Minami Y, Yatabe Y, Mitsudomi T, Tanaka H, Kimura T, Kudoh S, Nokihara H, Ohe Y, Yokota J, Uramoto H, Yasumoto K, Kiura K, Higashiyama M, Oda M, Saito H, Yoshida J, Kondoh K
Organizer
Annual Meeting
Place of Presentation
McCormick Place(USA.)
Year and Date
2011-06-04
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