| Project/Area Number |
16K19447
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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 |
Fukuda Koji 金沢大学, がん進展制御研究所, 助教 (10722548)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | EMT / miR-200 / ALK融合遺伝子陽性肺癌 / ALK / 薬剤耐性 / ALK肺がん |
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| Outline of Final Research Achievements |
ALK rearrangement, most commonly EML4-ALK, is detected in approximately 5% of non-small cell lung cancer (NSCLC). While ALK tyrosine kinase inhibitor (TKI) shows dramatic clinical efficacy in ALK-rearranged NSCLC patients, almost all patients acquire resistance over time. Epithelial mesenchymal transition (EMT) was also reported to be associated with various targeted drugs, however, its involvement in ALK-inhibitor resistance is largely unknown. We found that pre-treatment with Drug A can overcome the resistance by reverting EMT, in vitro and in vivo, due to up-regulation of miR-200c. The results of drug screening on a 200 kinase inhibitor library showed that 5 drugs increased E-cadherin expression of the resistant cells. These findings indicate that chemical restoration of miR-200c could be useful to circumvent resistance due to EMT in ALK-rearranged NSCLC.
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