Exploring a novel therapy for canine malignant melanoma by targeting ROCK signalling

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20614
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Takahashi Yosuke 東京大学, 大学院農学生命科学研究科(農学部), 特任研究員 (50912549)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: 犬悪性黒色腫 / 転移

Outline of Final Research Achievements

Canine malignant melanoma is a metastatic tumor and, due to the lack of effective systemic therapy, even after surgical resection of the lesion, the disease subsequently metastasises and the prognosis is short - less than one year - and therefore the establishment of a new systemic therapy is required. In this study, we identified PDPN-Rho-ROCK as a novel metastatic mechanism of canine malignant melanoma and elucidated its detailed signalling mechanism. Furthermore, we found that inhibition of PDPN-Rho-ROCK signalling in canine malignant melanoma cell lines can reduce the metastatic potential. Therefore, we have shown that inhibitors of the PDPN-Rho-ROCK signalling pathway may be useful in the development of new systemic therapies for canine malignant melanoma.

Free Research Field

獣医腫瘍学

Academic Significance and Societal Importance of the Research Achievements

犬の悪性黒色腫はとくに口腔内に発生が多く、口腔腫瘍の中で最も発生頻度が高い。大部分の症例が外科手術や放射線療法等の局所療法を行っても早期のリンパ節転移や肺転移のために、発症後1年以内に死に至る。現状では、犬において有効な化学療法や免疫療法がなく、全身投与により転移細胞を死滅させることが可能な、新たな治療法の開発が切望されている。本研究では、犬悪性黒色腫において、PDPN-Rho-ROCKシグナルが転移機構に関与しており、その阻害薬が新たな全身療法の確立に有用である可能性を示した。