| Project/Area Number |
18K15296
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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 | National Cancer Center Japan |
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Principal Investigator |
Yagishita Shigehiro 国立研究開発法人国立がん研究センター, 研究所, 研究員 (80781674)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | PDX / 遺伝子異常 / 非小細胞肺がん / 臨床効果予測 / 分子表的治療薬 / 遺伝子変異 / EGFR / ALK / 耐性 |
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| Outline of Final Research Achievements |
From a total of 245 lung cancer specimens, we successfully generated PDXs for 4 small cell lung cancer (engraftment rate: 38%) and 65 non-small cell lung cancer (engraftment rate: 21%) PDXs. The number of PDXs and its engraftment rate with clinical gene abnormalities were 7 EGFR (16%), 5 ALK (21%), 1 ROS1 (33%), 0 MET skipping (0%), 1 RET (25%), and 1 HER2 gene amplification (100%). We compared the clinical efficacy of the five genetically aberrant PDXs with that of the original patients, and found that some strains were concordant and some were discordant. The differences in efficacy were confirmed even in unapproved drugs, and while this is a useful basis for evaluation, the dosage needs to be optimized.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究開発において構築された基盤は、遺伝子異常を有する非小細胞肺がんにおける薬効評価基盤として活用可能であることが示唆された。また、薬剤耐性期のPDXは耐性後の治療戦略の構築や創薬開発研究に有用であることが期待される。一方で、PDXを用いた臨床効果予測に関しては、評価方法の最適化が必要と考えられ、さらなる検討が必要である。
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