| Project/Area Number |
17K09657
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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 |
Respiratory organ internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
GOTO Hisatsugu 徳島大学, 大学院医歯薬学研究部(医学域), 非常勤講師 (00437641)
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| Co-Investigator(Kenkyū-buntansha) |
荻野 広和 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (20745294)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 血管新生阻害薬耐性 / 肺癌 / 悪性胸膜中皮腫 / 血小板由来成長因子 / 血管新生 / 肺がん / 薬剤耐性 / 線維細胞 / 癌 |
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| Outline of Final Research Achievements |
The objective of this project was to explore the possibility of fibrocytes as the cellular biomarker of the resistance against anti-angiogenic therapy.
The study using mouse models revealed that; 1) inhibiting FGF2 which was produced by fibrocytes in addition to VEGF induced secondary resistance, and other angiogenic molecules such as PDGF might contribute to such resistance. 2) in the time course experiment, the number of fibrocytes in the tumor was significantly decreased within 3 days after the cessation of anti-VEGF treatment, suggesting that the interval of treatment might be crucial to minimize the resistance. The clinical study in lung cancer patients showed that the number of fibrocytes in the pleural effusion was significantly increased in 62% of patients who acquired the resistance to the treatment with anti-VEGF antibody, suggesting that fibrocytes in the pleural effusion might be useful as cellular biomarker to predict the resistance aganst anti-angiogenic therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
血管新生阻害薬を用いた抗血管新生療法は、様々ながん種で効果を発揮する一方、他の分子標的治療薬と同様に耐性化現象が問題視されている。最近我々は血管新生阻害薬耐性に関わる重要な細胞として線維細胞（fibrocyte）を同定した。血管新生阻害薬投与後の腫瘍内線維細胞の動態を明らかにすることで、線維細胞の集積を最小限にしつつ、血管新生阻害効果を維持する投与レジメンを提案できる可能性がある。また、胸水中の線維細胞を解析することで、腫瘍組織を採取することなく最小限の侵襲で血管新生阻害薬耐性化をモニターできるため、今後の癌治療に貢献できる可能性がある。
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