2021 Fiscal Year Final Research Report
Single-cell analyses reveal diverse mechanisms of resistance to EGFR-TKI in lung cancer
| Project/Area Number |
19K16879
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | The University of Tokyo (2020-2021)
National Cancer Center Japan (2019) |
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Principal Investigator |
Kashima Yukie 東京大学, 大学院新領域創成科学研究科, 特任助教 (80831883)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | シングルセル解析 / がん不均一性 / EGFR-TKI / オシメルチニブ / 薬剤耐性 |
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| Outline of Final Research Achievements |
EGFR-TKI, EGFR-tyrosine kinase inhibitor, is a promising therapy in EGFR-mutated lung cancer, but acquisition of resistance during treatment has been reported. In this study, we investigated the mechanism of drug resistance using EGFR-TKI inhibitors, osimertinib and erlotinib, by analyzing the process of drug resistance at the single-cell level longitudinally, using model lung cell lines and clinical biopsy samples. The analysis of model cell lines demonstrated some genes be involved in acquiring drug resistance. Those genes were also implicated in some clinical cases of drug resistance. The results of this study were published in an international peer-reviewed journal (Kashima et al, Cancer Research, 2021).
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| Free Research Field |
シングルセル解析
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| Academic Significance and Societal Importance of the Research Achievements |
日本人の非小細胞がん患者ではEGFR変異が、50%の割合を占めることが先行論文で報告されている。EGFR-TKIの耐性獲得に関しては、基礎実験、臨床検体の解析、バルクレベルのNGS解析等からいくつかの経路が示唆されてきたが、多層オミクスを利用した解析や不均一性に着目した研究は数が限られていた。本研究の成果は、一細胞RNA-seqと一細胞ATAC-seqを利用し、がんの不均一性や経時変化に着目し、薬剤耐性獲得の過程を明らかにした。これらの結果は、今後の個別化医療や創薬研究においても基盤となるデータになりうるという意味で高い社会的意義を持つと考えられる。
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