2020 Fiscal Year Final Research Report
The study of the impact of BET inhibition on NHEJ DNA damage repair and a new treatment strategy using BET inhibitors for lung cancer
Project/Area Number |
19K23876
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0901:Oncology and related fields
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Research Institution | Hokkaido University |
Principal Investigator |
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | 肺癌 / DNA修復 / 非相同末端結合 / BET |
Outline of Final Research Achievements |
We show that combined inhibition of BET and WEE1 synergistically suppresses NSCLC growth. BET inhibition considerably repressed NHEJ pathway-related genes and diminished NHEJ pathway-mediated DNA double-strand break repair. Furthermore, BET inhibition repressed MYT1 expression and promoted mitotic entry when combined with WEE1 inhibition. This is the first report to show that BET inhibition synergizes with WEE1 inhibitor via two distinct mechanisms, impairing NHEJ DNA damage repair and synergistic forced mitotic entry.
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Free Research Field |
肺癌
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Academic Significance and Societal Importance of the Research Achievements |
過去の報告はBET阻害によるHR機構抑制を対象としたものがほとんどだが、本研究ではもう一つのDNA2本鎖切断修復機構であるNHEJ機構を対象とした。BET阻害によるNHEJ阻害を抗癌治療に応用できれば、幅広いDNA傷害性薬剤の作用を増強することが期待でき、新たな抗癌治療の開発につながる。非小細胞肺癌細胞を用いてBET阻害によるNHEJ機構抑制能を明らかにし、機序も検討した本研究は今後の非小細胞肺癌の治療開発の一助となる可能性がある。
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