2023 Fiscal Year Final Research Report
Development of lung cancer treatment targeting drug tolerance by SHP2.
| Project/Area Number |
21K08179
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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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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
久保 寿夫 岡山大学, 大学病院, 助教 (90726928)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 肺癌 / 分子標的治療 / tolerance / SHP2 / RB |
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| Outline of Final Research Achievements |
The role of SHP2 in tolerance to molecularly targeted lung cancer therapies was investigated using lung cancer cell lines with ALK, ROS1 and EGFR gene abnormalities. Using cell line and subcutaneous tumour mouse models, we showed that cancer cells that remained tolerant under exposure to the respective molecular-targeted therapies were significantly inhibited by SHP2 inhibition. Furthermore, SHP2 maintains cell cycle-associated factor RB activity and induces tolerance by maintaining the cell cycle under molecularly-targeted therapy. Inhibition of SHP2 under exposure to molecularly targeted therapies strongly suppressed RB activity. Inhibition of the cell cycle-associated factor CDK4/6 inhibited tolerance as well as SHP2 inhibition.
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| Free Research Field |
肺癌
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により肺がん分子標的治療における薬剤toleranceにおいてSHP2が重要な役割を果たすことが明らかとなった．SHP2を標的とすることで、肺がん分子標的治療においてこれまで困難とされていた根治的効果を持つ治療開発につながる可能性がある．
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