Elucidation of drug sensitivity control mechanism to enhance the therapeutic effect of cetuximab on oral cancer
| Project/Area Number |
17K17267
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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 |
Surgical dentistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
NARUSE Tomofumi 長崎大学, 医歯薬学総合研究科(歯学系), 客員研究員 (70549609)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | セツキシマブ / アルペリシブ / 口腔癌 / 耐性 / PIK3CA / PI3Kp110α / PIK3CA遺伝子 / セツキシマブ耐性 / 口腔扁平上皮癌 / 上皮間葉転換 / EGFR |
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| Outline of Final Research Achievements |
The present study aimed to examine the association of PI3Kp110α pathway expression with cetuximab resistance and the anti-tumor effects of alpelisib (PI3K inhibitor) and cetuximab in oral squamous cell carcinoma (OSCC) cells.
PI3Kp110α expression was significantly associated with the tumor response to cetuximab (p < 0.05) and one-year PFS and OS. Combined treatment with alpelisib and cetuximab resulted in enhanced anti-tumor effects in vitro compared to either agent treated individually. In particular, expression of EMT-related proteins decreased, suggesting that the invasion potential of cetuximab-resistant cells decreased. Furthermore, treatment of mice bearing OSCC xenografts with alpelisib and cetuximab decreased PI3K pathway expression.
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| Academic Significance and Societal Importance of the Research Achievements |
セツキシマブ療法は再発/転移口腔癌の標準治療として普及している。奏効率は高く、一定の生存期間の延長が期待でき、我々もその治療成績について欧文雑誌で公表している。しかしながら、長期投与に伴う薬剤耐性も問題となっており、セツキシマブ以降の治療選択肢については科学的根拠の高いものがほとんどない。本研究ではそのセツキシマブ薬剤耐性を克服するための研究を行い、一定の成果を出すことができた。これが実臨床に応用されれば、再発/転移口腔癌の生存期間のさらなる延長が期待でき、社会的意義は十分にあると考える。
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Report
(4 results)
Research Products
(1 results)
