Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations
| Project/Area Number |
23790902
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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 |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肺癌 / 分子標的治療 / EGFR変異 / 足場蛋白質 / 薬剤耐性 / EGFR / がん分子標的 / 上皮成長因子受容体 |
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| Research Abstract |
We focused on Akt kinase-interacting protein1 (Aki1), a scaffold protein of PI3K /PDK1/Akt, and assessed its role in EGFR mutant lung cancer. Aki1 constitutively associates with mutant EGFR in lung cancer cells. Silencing of Aki1 inhibited cell growth of EGFR mutant lung cancer cells and induced apoptosis of them. Treatment with Aki1 siRNA dramatically inhibited growth of EGFR mutant lung cancer cells in a xenograft model. Moreover, Aki1 was frequently expressed in tumor cells of EGFR mutant lung cancer patients, including those with acquired resistance to EGFR-TKI treatment. Our data suggest that Aki1 may be an ideal target for EGFR mutant lung cancer patients, especially those with acquired EGFR-TKI resistance due to EGFR T790M gatekeeper mutation.
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Report
(3 results)
Research Products
(44 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
Issue: 6
Pages: 1663-71
DOI
Related Report
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
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Journal Title
Am J Pathol
Volume: 181
Issue: 3
Pages: 1034-1043
DOI
Related Report
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
Issue: 11
Pages: 3619-30
DOI
Related Report
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
Issue: 7
Pages: 1218-28
DOI
Related Report
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
Issue: 3
Pages: 1483-93
DOI
Related Report
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
Issue: 12
Pages: 2011-7
DOI
Related Report
Peer Reviewed
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