2014 Fiscal Year Final Research Report
The new strategy for lung cancer treatment by Hsp90 inhibitors and radiation therapy
Project/Area Number |
24791462
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Thoracic surgery
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | 原発性肺癌 / Hsp90阻害剤 / 放射線治療 / EGFRチロシンキナーゼ阻害剤耐性 |
Outline of Final Research Achievements |
We evaluated the radiosensitizing effect of Hsp90 inhibitor, NVP-AUY922 (AUY), on NSCLC cell lines harboring EGFR activating mutations and showing acquired resistance to EGFR-TKIs via any of several mechanisms. AUY was more effective against the gefitinib-resistant sublines with T790M mutation and MET amplification than against the parental cell lines, although the subline with stem cell-like properties showed more than a 10-fold higher resistance to AUY than the parental cell line. AUY exerted a significant radiosensitizing effect on the parental cell line and the MET-amplified subline through inducing G2/M arrest and inhibition of non-homologous end joining (NHEJ). In contrast, the radiosensitizing effect of AUY was limited on the subline with stem cell-like properties, in which it did not induce G2/M arrest or inhibition of NHEJ.
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Free Research Field |
呼吸器外科学
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