| Project/Area Number |
26830118
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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 |
Tumor therapeutics
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
Ochi Nobuaki 川崎医科大学, 医学部, 講師 (80611615)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKIGAWA Nagio 川崎医科大学, 総合内科学4, 教授 (60325107)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 非小細胞肺癌 / pemetrexed / EGFR-TKI / 耐性 / EGFR / ペメトレキセド / 耐性化 / thymidylate synthase |
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| Outline of Final Research Achievements |
Pemetrexed is a key drug in the treatment for the patients with activating EGFR mutation-positive non-small cell lung cancer (NSCLC). However, the relationship between TS up-regulation and EGFR mutation status and the difference of resistant mechanisms among a variety of EGFR mutations remain unclear. We previously reported that TS and dihydrofolate reductase were involved in developing PEM resistance in PC-9 (EGFR exon19 in-frame deletion mutation) and A549 (wild-type EGFR) cells. In this study, TS is significantly up-regulated in H1975 (L858R+T790M mutation) cells. Moreover, epithelial-mesenchymal transition might be an alternative resistant mechanism in H1975 cell. Meanwhile, the sensitivity to EGFR-tyrosine kinase inhibitor was increased in EGFR-mutation positive-PEM resistant cells. These results warrant further preclinical studies and the optimal treatment sequence in EGFR mutation-positive NSCLC patients will be projected.
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