| Project/Area Number |
16K20581
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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 | Yamaguchi University |
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Principal Investigator |
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| Research Collaborator |
HARADA Koji
HISANO Takahiro
FUJIWARA Rieko
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | PD-1 / 5-FU / cisplatin / cetuximab / drud resistance / PD-1抗体 / 5-FU耐性 / Cisplatin耐性 / Cetuximab耐性 / マウスPD-1抗体 / シスプラチン / Cetuximab / 併用療法 / 免疫チェックポイント阻害剤 / 抗PD-1抗体 / 抗癌剤 / アポトーシス / 口腔扁平上皮癌 |
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| Outline of Final Research Achievements |
We established anticancer agent (5-FU or Cisplatin; CDDP)-resistant or molecular-targeted agent (Cetuximab; CET)-resistant oral squamous cell carcinoma cells to develop each drug-resistant tumors. 5-FU, CDDP or CET -resistant tumors showed low sensitivity to each agent. Then these tumors were treated with immune check point inhibitors (anti-PD-1 antibody; ICPI) alone or in combination with 5-FU, CDDP or CET. Single-agent administration of ICPI showed moderate level of antitumor effect against each type of resistant tumors. Moreover, ICPI in combination with 5-FU, CDDP or CET showed enhanced antitumor effect than each agent alone. Among all of these drug combinations, ICPI showed the highest level of anti-tumor effect in combination with CET than 5-FU or CDDP. Above findings suggested that, single-agent administration of ICPI could be effective against drug-resistant tumors, and its antitumor effect could be further enhanced when combined with other anticancer agents.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果から、薬剤耐性腫瘍に対しても免疫チェックポイント阻害剤は抗腫瘍効果を発現可能であり、抗癌剤や分子標的治療薬との併用ではさらに抗腫瘍効果が増強される可能性が示唆された。免疫チェックポイント阻害剤ニボルマブの１サイクルの治療費は当初5000万円、薬価が下がった現状でさえも2000万円近くまで必要である。またニボルマブが第一選択として使用できない現状では、ニボルマブの奏功率は20%程度でしかない。そこで医療経済学的観点から、また臨床的有用性の点からも、難治性口腔癌に対する適切な治療レジメンの開発が望まれるが、単剤投与では限界があるが、抗癌剤や分子標的薬との併用療法は今後大きく期待できる。
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