Development of novel molecular targeted therapy for canine prostate cancer based on blockade of MAPK/ERK signaling pathway

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15383
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Kobayashi Masanori 日本獣医生命科学大学, 獣医学部, 講師 (80600428)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 犬 / 前立腺癌 / 分子標的治療

Outline of Final Research Achievements

The purpose of this study is to clarify whether blockade of MAPK/ERK signaling pathway may exert anti-tumor effect on canine prostate cancer with BRAF V450E mutation. Selective inhibition of RAF, MEK and ERK, which compose the MAPK/ERK signaling pathway, suppressed the proliferation of canine prostate cancer cells in vitro. In addition, RAF and MEK inhibitors produced tumor growth inhibitory or contracting effects in vivo without causing severe side effects. These results suggest that the BRAF mutation is a driver mutation involved in the growth and survival of canine prostate cancer cells, and blockade of the MAPK/ERK signal transduction pathway may be a new molecular targeted therapy for canine prostate cancer.

Free Research Field

獣医臨床繁殖学

Academic Significance and Societal Importance of the Research Achievements

犬前立腺癌は悪性腫瘍であり早期に局所浸潤や遠隔転移を引き起こすが、著効を示す治療法が確立されていない。本研究では、BRAF変異を有する犬前立腺癌に対するMAPK/ERKシグナル伝達経路の遮断によって腫瘍の増殖を抑制することが明らかにし、犬前立腺癌の新たな全身治療法の可能性が提示できたものと考えられる。犬前立腺癌のみならず獣医領域において同様のBRAF変異を持つ移行上皮癌などの他の腫瘍に対して、また前立腺癌が自然発症するヒトに対しても有益な情報をもたらすことができるだろう。