Development of drug-resistance-overcoming agents targeting histone demethylase JARID1A

2015 Fiscal Year Final Research Report

• Project/Area Number: 25640093
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: Tamio Mizukami 長浜バイオ大学, バイオサイエンス学部, 教授 (80367896)
• Research Collaborator: SASAKI Ryuzo 長浜バイオ大学, バイオサイエンス学部, 客員教授 (60077378) ; HASEGAWA Makoto 長浜バイオ大学, バイオサイエンス学部, 教授 (10367899) ; NAGAI Nobuo 長浜バイオ大学, バイオサイエンス学部, 教授 (90260281) ; Wada Shuichi 長浜バイオ大学, バイオサイエンス学部, 准教授 (20378607) ; SUZUKI Takayoshi 京都府立医科大学, 医学研究科医薬品化学講座, 教授 (90372838) ; MIYATA Naoki 名古屋市立大学, 大学院薬学研究科薬化学分野, 教授 (50114674) ; Yoshida Minoru 理化学研究所基幹研究所, 吉田化学遺伝学研究室, 主任研究員 (80191617) ; Itoh Akihiro 理化学研究所基幹研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 分子標的治療

Outline of Final Research Achievements

Histone lysine methylation status is well controlled by histone lysine-specific methyltransferases and demethylases. This control plays a crucial role in the epigenetic gene expression and is frequently involved in cell proliferation and survival in cancer. JARID1A is a histone demethylase whose substrates are H3K4me2/me3. JARID1A has been reported as a drug-resistance-causing molecule in 2010; overexpression of JARID1A allowed cancer cells to acquire drug resistance, whereas knockdown of JARID1A expression by RNA interference sensitized drug resistance. These results suggest that JARID1A is an interesting drug discovery target for drug-resistance-overcoming agents. In this study, we attempted to develop JARID1A inhibitors as epigenomic drugs that have drug-resistance-overcoming activity.

Free Research Field

腫瘍治療学