Development of ALK-TKI-resistant treatment due to EMT of ALK lung cancer
Project/Area Number |
16K19447
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Respiratory organ internal medicine
|
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
|
Project Status |
Completed (Fiscal Year 2017)
|
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)
|
Keywords | EMT / miR-200 / ALK融合遺伝子陽性肺癌 / ALK / 薬剤耐性 / ALK肺がん |
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.
|
Report
(3 results)
Research Products
(5 results)
-
[Presentation] Heterogeneity of epithelial-to-mesenchymal transition and resistance mutation in ALK inhibitor-resistant lung cancer and its circumvention2018
Author(s)
Koji Fukuda, Shinji Takeuchi, Sachiko Arai, Ryohei Katayama, Shigeki Nanjo, Azusa Tanimoto, Akihiro Nishiyama, Takeshi Suzuki, Kengo Takeuchi, Makoto Nishio, Seiji Yano.
Organizer
Fifth AACR-IASLC International Joint Conference
Related Report
Int'l Joint Research
-
[Presentation] Heterogeneity of epithelial-to-mesenchymal transition and resistance mutation in ALK inhibitor-resistant lung cancer and its circumvention2018
Author(s)
Koji Fukuda, Shinji Takeuchi, Sachiko Arai, Ryohei Katayama, Shigeki Nanjo, Azusa Tanimoto, Akihiro Nishiyama, Takeshi Suzuki, Kengo Takeuchi, Makoto Nishio, Seiji Yano.
Organizer
The 1st NanoLSI International Symposium
Related Report
Int'l Joint Research
-
-
-