2023 Fiscal Year Final Research Report
Novel therapeutic strategy for canine urothelial carcinoma: cancer elimination by anti-inflammation with BRAF inhibitor
| Project/Area Number |
19K15976
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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 42020:Veterinary medical science-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | イヌ尿路上皮癌 / BRAF阻害薬 / ダブラフェニブ |
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| Outline of Final Research Achievements |
The purpose of this study was to establish a new cancer therapy using BRAF inhibitors in canine urothelial carcinoma (UC) and to analyze gene expression of UC cells in urine.
Seven dogs with BRAF mutation-positive UC who presented to Hokkaido University Veterinary Hospital were treated with dabrafenib (5 mg/kg/day). Clinical efficacy was observed in 1 case of PR, 5 cases of SD, and 1 case of PD, and clinical improvement was achieved in many cases. Four cases had skin masses that appeared to be side effects, but none required dose reduction or discontinuation. These results suggest that dabrafenib may be useful for UC. RNA were also extracted from tumor cells in urine collected before and at the end of the clinical trial.
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| Free Research Field |
獣医腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
イヌ尿路上皮がん(UC)は、内科療法への反応率の低さや耐性の発現などにより予後不良の疾患とされており、新たな治療法の確立が求められている。BRAF阻害薬であるダブラフェニブを担癌犬に投与した報告はなくその有用性は不明であったが、本研究によりダブラフェニブのイヌにおける安全性、イヌUCに対する有用性が示され、イヌでもヒトと同様の副作用がみられることが明らかとなった。さらなる調査によりイヌUCの新たな治療法となることが期待される。また、イヌUCは疫学や臨床的特徴が類似していることからヒトUCのモデルとして用いられる。そのため、本研究結果は一部のヒトUCに対しても有益な結果となりうる。
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