| Project/Area Number |
26293196
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
|
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| Research Institution | Saitama Medical University (2015-2016)
Niigata University (2014) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
矢野 聖二 金沢大学, がん進展制御研究所, 教授 (30294672)
梅津 哉 新潟大学, 医歯学総合病院, 准教授 (50251799)
土田 正則 新潟大学, 医歯学系, 教授 (60293221)
|
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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 |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | DDX3X / Wnt/β-catenin / VEGF / EGFR遺伝子変異陽性肺癌 / PD-1 / EGFR / 肺癌 / beta-catenin / VEGFR / β-catenin / 癌幹細胞 |
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| Outline of Final Research Achievements |
EGFR-TKI has led to unprecedented results in lung cancer patients harboring activating EGFR mutations. However, the phenotypic diversity of cancer cells results in the survival of treatment-resistant cells. DDX3X is a RNA helicase and is involved in Wnt/β-catenin signal activation. We identified lung cancer cells that expressed DDX3X achieve cancer stem cell-like and mesenchymal properties resulting in EGFR-TKI resistance. Response rate of DDX3X positive EGFR mutant lung cancer patients was only 13.3 %. In this study, we demonstrated that Wnt/β-catenin or VEGFR signal inhibitors exhibited synergistic antitumor reactivity to break EGFR-TKI resistance. Clinical sample analyses revealed that DDX3X expression was accompanied withβ-catenin and VEGFR-2 expression. Our data indicate a novel mechanism how lung cancer cells harboring EGFR-activating mutations survive through EGFR-TKI treatment and have a clinical implication to develop a novel treatment for VEGFR- and β-catenin-signaling.
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