The utility of cancer therapy targeting DNA damage repair system against gastrointestinal cancer
| Project/Area Number |
16K09287
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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 |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
KUBOTA EIJI 名古屋市立大学, 大学院医学研究科, 准教授 (30405188)
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| Co-Investigator(Kenkyū-buntansha) |
片岡 洋望 名古屋市立大学, 大学院医学研究科, 准教授 (40381785)
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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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | DNA修復機構 / 消化管癌 / 大腸がん / ATM / ATR / 腫瘍免疫療法 / 消化器癌 |
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| Outline of Final Research Achievements |
In this study, we investigated the usefulness of novel therapies for gastrointestinal cancers targeting ATM and ATR, which play crucial role in DNA repair mechanisms. We found that inhibition of ATM and Chk1, a downstream factor of ATR, alone had antitumor effects and enhanced the effects of L-OHP, a conventional antitumor drug. Combinations of ATM and Chk1 inhibitors showed synergistic antitumor effects, and in vivo studies have shown that drugs that target these DNA repair mechanisms may induce tumor immunity. In this study, the usefulness of KRAS and BRAF gene mutations as biomarkers for anticancer drugs targeting DNA repair mechanisms was not clear.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、DNA修復機構を標的とした新規抗腫瘍薬が消化管癌に対して有効であることを示した。またDNA修復機構を標的とした薬剤が、単独での抗腫瘍効果だけではなく既存の抗がん剤に対する増感作用を有することや、最近注目されている腫瘍免疫の誘導作用をも有することを明らかとした。本研究でえられた知見は、消化管癌に対する新規治療薬の開発に寄与できるものと考えられる。
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Report
(4 results)
Research Products
(1 results)
