| Project/Area Number |
26860595
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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 | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 薬剤耐性 / ALK肺癌 / Src阻害薬 / アレクチニブ / サラカチニブ / セリチニブ / ロラチニブ / ALK rearrangement / ROS1 rearrangement / Src inhibitor |
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| Outline of Final Research Achievements |
ALK tyrosine kinase inhibitors (TKIs) play a significant role in the treatment of ALK rearranged non-small cell lung cancer patients. After the significant response to ALK-TKIs, the emergence of acquired resistance occurs for all patients. Understanding the origin of resistance mechanisms within a patient is crucial to guide treatment and developing drugs/combinations to circumvent resistance. There are reported that some of the tyrosine kinases are involving by bypassing ALK signaling, but comprehensive identification of proteins that are significant for acquired resistance in ALK-TKIs is still required.
Our results revealed that Crk-Src related proteins were overexpressed in ALK TKI resistance cells and had a significant protein expression changes. To address the impact of overcoming resistance by blocking Crk-Src pathway, Drugs/combinations with ALK inhibitor and/or Src inhibitors showed that significant treatment effect in vitro and in vivo study using tumor-bearing mouse model.
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