Analysis of oncogene addiction and development of molecular-targeted therapy for small animal tumours

2014 Fiscal Year Final Research Report

• Project/Area Number: 24380173
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Clinical veterinary science
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: BONKOBARA Makoto 日本獣医生命科学大学, 獣医学部, 准教授 (50343611)
• Co-Investigator(Kenkyū-buntansha): TAZAKI Hiroyuki 日本獣医生命科学大学, 獣医学部, 教授 (80231405) ; OMI Toshinori 日本獣医生命科学大学, 獣医学部, 教授 (40296091) ; TOMIHARI Mizuki 帯広畜産大学, 畜産学部, 講師 (00552754)
• Co-Investigator(Renkei-kenkyūsha): SHIMADA Takashi 日本医科大学, 医学部, 教授 (20125074)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 犬 / 組織球性肉腫 / oncogene addiction / キナーゼ / ダサチニブ

Outline of Final Research Achievements

To establish foundation of molecular-targeted therapy for small animal tumours, we sought canine tumour-derived cell lines that have “oncogene addiction” and analysed signalling pathway(s) on which they depend. A kinase inhibitor, dasatinib, was found to have potent growth inhibitory activity against some histiocytic sarcoma (HS) lines in vitro and in vivo. We then performed kinome analysis using HS lines and found that 14-3-3 protein gamma is constitutively activated in some HS lines that are sensitive to dasatinib. Because 14-3-3 protein gamma does not have kinase activity, it was considered that dasatinib targeted kinase in upper JNK pathway. From these findings, dasatinib could be a potential therapeutic drug for certain HS cases whose tumour cells have constitutively phosphorylated 14-3-3 protein gamma.

Free Research Field

獣医臨床病理学