2023 Fiscal Year Final Research Report
Elucidating the mechanisms of drug-tolerant cell formation in EGFR lung cancer
| Project/Area Number |
19K23930
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Okayama University (2020, 2022-2023)
National Cancer Center Japan (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2024-03-31
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| Keywords | EGFR肺癌 / β-catenin / Drug-tolerant persisters |
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| Outline of Final Research Achievements |
β-catenin, one of the key players in Wnt signalling, is known to play an important role in tumour development in colorectal cancer, etc. However, its role in lung cancer remains unclear. Our previous studies have shown that β-catenin is essential for lung tumourigenesis by active EGFR and that β-catenin binds directly to active EGFR and is tyrosine-phosphorylated.We found that the YAP-TBX5 pathway, which is different from the classical pathway, showed increased activity in the presence of active EGFR. The Src-family pathway is also activated in the presence of active EGFR, suggesting that phosphorylation of β-catenin-Y333 tyrosine residues by the Src family may cause a molecular switch from the classical pathway to the YAP-TBX5 pathway. βcatenin-YAP-TBX5 pathway regulates anti-apoptosis-related genes such as the BcL2L1 gene, and suppression of these pathways may be a new therapeutic target in addition to the strategy of suppressing EGFR activity with EGFR-TKI.
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| Free Research Field |
肺癌
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| Academic Significance and Societal Importance of the Research Achievements |
活性型EGFR遺伝子変異陽性肺癌において、Drug-tolerant persisters(DTPs)形成の詳細なメカニズムの一端を明らかにし、DTPs形成阻害による、耐性克服の新たな治療方法創出が可能であることを示した。
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