2017 Fiscal Year Final Research Report
Development of ALK-TKI-resistant treatment due to EMT of ALK lung cancer
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 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Kanazawa University |
Principal Investigator |
Fukuda Koji 金沢大学, がん進展制御研究所, 助教 (10722548)
|
Project Period (FY) |
2016-04-01 – 2018-03-31
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Keywords | EMT / miR-200 / ALK融合遺伝子陽性肺癌 |
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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Free Research Field |
分子腫瘍学
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