Biomarker to predict the efficacy of inhibitors of EGFR tyrosine kinase in oral squamous cell carcinoma
| Project/Area Number |
16K11760
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Ohu University |
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Principal Investigator |
Baba Yuh 奥羽大学, 歯学部, 教授 (40597663)
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| Co-Investigator(Kenkyū-buntansha) |
高田 訓 奥羽大学, 歯学部, 教授 (40254875)
加藤 靖正 奥羽大学, 歯学部, 教授 (50214408)
藤井 正人 独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 研究員 (70129633)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 口腔癌 / EGFR / PIK3CA / AKT / バイオマーカー / デグエリン / 食道癌 / EGFR阻害剤 |
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| Outline of Final Research Achievements |
In this study, we aimed to study whether combinatorial treatment using AG1478(EGFR tyrosine kinase inhibitor) and deguelin could enhance the anti-tumor effects of AG1478 in oral squamous cell carcinoma(SCC). For Ca9-22 cells with PIK3CA wild types, AG1478 alone suppressed AKT and induced apoptosis. On the contrary, for HSC-4 cells with PIK3CA mutant, AG1478 alone did not suppress the phosphorylated level of AKT nor induce apoptosis. Forced expression of constitutively active PIK3CA (G1633A mutation) significantly reduced the apoptotic effect of AG1478 on the PIK3CA wild-type Ca9-22 cells. When HSC-4 cells with the PIK3CA G1633A mutation were treated with a combination of AG1478 and deguelin, combination effects on apoptosis induction were observed through theinhibition of the AKT pathway. These results suggest that the combination of EGFR tyrosine kinase inhibitor with deguelin is a potential therapeutic approach to treat PIK3CA-mutated oral SCC.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔扁平上皮癌の90％以上に上皮成長因子受容体Epidermal growth factor receptor(EGFR)が過剰発現しており、EGFRシグナル伝達系は口腔癌における重要な治療標的である。これまで、切除不能な進行・再発口腔癌において放射線療法や化学療法に対するEGFR阻害剤の上乗せ効果が証明されているが、EGFR阻害剤の効果を予測する因子に関してはいまだに不明であった。本研究によって口腔癌に対するEGFR阻害剤の効果予測因子の一つがPIK3CA遺伝子変異であることが明らかになり、口腔癌に対する個別化医療の可能性が期待される。
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Report
(4 results)
Research Products
(19 results)
