| Project/Area Number |
16K18462
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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 |
Tumor therapeutics
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肺癌 / HER2遺伝子変異 / 薬剤感受性 / 耐性２次変異 / HER2変異肺癌 / YVMA / Poziotinib / Neratinib / 耐性二次変異 / C805S / 原発性肺癌 / 癌 / 肺癌個別化治療 |
|---|
| Outline of Final Research Achievements |
Recently, a novel HER2 inhibitor, poziotinib has been developed and clinical trial results are being expected. We introduced HER2 mutations into Ba/F3 cells. Poziotinib activity was compared with 8 TKIs. We defined sensitivity index (SI) as an IC90 divided by trough concentration of a given drug at the recommended dose for humans in the literature. In addition, we created resistant clones by exposing poziotinib and HER2 secondary mutations were searched.
For most common A775_G776insYVMA(YVMA), poziotinib was the only drug that had SI of less than 10. We established 19 poziotinib-resistant clones, all of which harbored C805S secondary mutation of the HER2 gene.
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