2021 Fiscal Year Final Research Report
Analysis of diversity in tyrosine kinase inhibitor resistance in mast cell tumors toward establishment of individualized therapy
| Project/Area Number |
19H03131
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 42020:Veterinary medical science-related
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| Research Institution | Nippon Veterinary and Life Science University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 崇 札幌医科大学, 医学部, 講師 (50723897)
田崎 弘之 日本獣医生命科学大学, 獣医学部, 教授 (80231405)
呰上 大吾 東京農工大学, (連合)農学研究科(研究院), 准教授 (80453934)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 肥満細胞腫 / チロシンキナーゼ阻害剤 / 耐性化 / 個別化治療 |
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| Outline of Final Research Achievements |
This study indicates that accumulation of KIT mutations due to TK inhibitor exposure is important for TK inhibitor resistance in mast cell tumors, which results in TK inhibitor-resistant secondary mutations in KIT. In addition, it was shown that ultra-trace amounts of TK inhibitor-resistant clones may pre-exist in tumor tissues. On the other hand, although various mutations of KIT are detected in canine mast cell tumors, it was not possible to predict whether or not TK inhibitor resistance would occur based solely on the site and type of mutation. Therefore, it was considered that development of highly accurate and extensive genetic analysis system, such as next-generation sequencing analysis, for detection of KIT mutation and further functional characterization the mutant KIT proteins are important in order to establish individualized therapies to overcome TK inhibitor resistance.
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| Free Research Field |
獣医臨床病理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、犬の肥満細胞腫におけるチロシンキナーゼ阻害剤耐性化メカニズムの一端を明らかにした。また、この知見は耐性の克服に向けた新たな個別化治療の構築につながると考えられる。人においても同様の腫瘍が主に小児において発生し（人では肥満細胞症という）、チロシンキナーゼ阻害剤が奏功する場合がある。しかしながら、犬や猫の肥満細胞腫と同様に最終的に耐性が生じることが問題となっている。本研究から得られた成果は、小児肥満細胞症におけるチロシンキナーゼ阻害剤耐性の克服戦略の開発にも貢献する可能性が高く、社会的に重要な意義を持つ成果と考える。
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