2012 Fiscal Year Final Research Report
Development of novel targeted therapy for lung cancer with activating Ras mutation
| Project/Area Number |
23790903
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
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) |
2011 – 2012
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| Keywords | 肺がん / Ras / ROS |
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| Research Abstract |
There are still no effective targeted therapies for patients with K-ras activating mutations which is a cause of intrinsic resistance to EGFR-TKI. Here, we assessed therapeutic effect of β-phenylthyl isothiocynate (PEITC) on lung cancer cellswith K-ras activating mutations through production of reactive oxygen species (ROS).Treatment with PEITC reduced cell viability and induced apoptosis in K-ras mutant lung cancer cells. In a xenograft model, PEITC dramatically reduced tumor growth with less toxicity. Moreover, normal human fibloblasts and K-ras wild lung cancer cells weresignificantly less sensitive to PEITC. Our findings suggest that PEITC can selectively kill lung cancer cells with K-ras activating mutations.
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[Journal Article] The novel phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor, BEZ235, circumvents erlotinib resistance of epidermal growth factor receptor mutant lung cancer cells triggered by hepatocyte growth factor.2013
Author(s)
Sano T, Takeuchi S, Nakagawa T, Ishikawa D, Nanjo S, Yamada T, Nakamura T, Matsumoto K, Yano S
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Journal Title
Int J Cancer
Volume: 133
Pages: 505-13
DOI
Peer Reviewed
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[Journal Article] Combined therapy with mutant-selective EGFR inhibitor and Met kinase inhibitor for overcoming erlotinib resistance in EGFR-mutant lung cancer2012
Author(s)
Nakagawa T, Takeuchi S, Yamada T, Nanjo S, Ishikawa D, Sano T, Kita K, Nakamura T, Matsumoto K, Suda K, Mitsudomi T, Sekido Y, Uenaka T, Yano S
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Journal Title
Mol Cancer Ther
Volume: 11
Pages: 2149-57
DOI
Peer Reviewed
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[Journal Article] Dual inhibition of Met kinase and angiogenesis to overcome HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer2012
Author(s)
Takeuchi S, Wang W, Li Q, Yamada T, Kita K, Donev IS, Nakamura T, Matsumoto K, Shimizu E, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S
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Journal Title
Am J Pathol
Volume: 181
Pages: 1034-43
DOI
Peer Reviewed
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[Journal Article] Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells2012
Author(s)
Yamada T, Takeuchi S, Nakade J, Kita K, Nakagawa T, Nanjo S, Nakamura T, Matsumoto K, Soda M, Mano H, Uenaka T, Yano S
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Journal Title
Clin Cancer Res
Volume: 18
Pages: 3592-602
DOI
Peer Reviewed
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[Journal Article] Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer2012
Author(s)
Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, 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]2011
Author(s)
Ogino H, Hanibuchi M, Kakiuchi S, Trung VT, 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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[Presentation] Met/VEGFR-2阻害剤E7050は変異型EGFR肺がんにおいてHGFによるEGFR-TKI耐性誘導を克服する2011
Author(s)
竹内 伸司, Wang Wei, Li Qi, 山田 忠明, Donev Ivan, 小泉 瞳, 中村 隆弘, 松本 邦夫, 西岡 安彦, 曽根 三郎, 上仲 俊光, 矢野 聖二
Organizer
第70回日本がん学会学術総会
Year and Date
2011-10-03
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