| Project/Area Number |
26462003
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
Ito Yuichi 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (80397463)
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| Co-Investigator(Kenkyū-buntansha) |
中西 速夫 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (20207830)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | HER2陽性胃がん / FGFR2陽性胃がん / 細胞株パネル / ハーセプチン耐性株 / 耐性機構 / T-DM1 / 分子標的薬 |
|---|
| Outline of Final Research Achievements |
Among various types of gastric cancers, HER2-positive cancer proved to be effective target by trastuzumab (Tmab), but Tmab resistance remains a major problem to be resolved. In this study, we newly developed gastric cancer cell line panel including HER2 high/low gene amplified- and Tmab resistant cell lines and examined anti-tumor effect of T-DM1, Afatinib, an irreversible TKI and Tmab plus chemotherapy in mouse xenograft models. The results showed that T-DM1 and Afatinib alone and Tmab-paclitaxel combination exhibited significant anti-tumor effect against Tmab-resistant cell lines through different molecular mechanisms. In addition, we developed FGFR2 gene-amplified gastric scirrhous cancer cells and examined the effect of a new TKI for FGFR2 (PD173074), showing significant anti-tumor effect against FGFR2-positive cells. These results suggest a new treatment modality consisting of molecular targeting therapies and surgery against HER2-positive and FGFR2-positive gastric cancers.
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