Taking advantage of a pitfall in glioma cancer stem cell epigenetics to develop novel therapies directed to cancer stem cells

• Project/Area Number: 16K15640
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Yamagata University
• Principal Investigator: KITANAKA Chifumi 山形大学, 医学部, 教授 (70260320)
• Co-Investigator(Renkei-kenkyūsha): OKADA MASASHI 山形大学, 医学部, 講師 (70512614)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: glioma-initiating cells / Tumor-initiating cells / Tumor-initiating cell / グリオーマ

Outline of Final Research Achievements

Cancer stem cells are a small subpopulation of immature, undifferentiated tumor cells characterized by therapy resistance as well as by their ability to initiate tumors on one hand and on the other to undergo differentiation into mature, non-cancer stem cells that no longer retain therapy resistance or tumor-initiating capacity. As such, cancer stem cells are deemed a major culprit of post-treatment tumor recurrence and therefore a key therapeutic target in the development of curative cancer therapies. Here in this research project, we tested our original working hypothesis that tri-methylation at H3K27 promotes the differentiation of glioma stem cells, an idea apparently paradoxical to what has been widely believed in the field of glioma stem cell research, in an attempt to develop novel therapies directed against glioma stem cells.

Research Products

• [Journal Article] Repositioning CEP-1347, a chemical agent originally developed for the treatment of Parkinson's disease, as an anti-cancer stem cell drug. (2017)
  • Author(s): Okada M, Takeda H, Sakaki H, Kuramoto K, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C.
  • Journal Title: Oncotarget. Volume: 8 Issue: 55 Pages: 94872-94882
  • DOI: 10.18632/oncotarget.22033
  • Peer Reviewed / Open Access
• [Journal Article] Licochalcone A specifically induces cell death in glioma stem cells via mitochondrial dysfunction. (2017)
  • Author(s): Kuramoto K, Suzuki S, Sakaki H, Takeda H, Sanomachi T, Seino S, Narita Y, Kayama T, Kitanaka C, Okada M.
  • Journal Title: FEBS Open Bio. Volume: 7 Issue: 6 Pages: 835-844
  • DOI: 10.1002/2211-5463.12226
  • Peer Reviewed / Open Access
• [Journal Article] Impact of H3K27 Demethylase Inhibitor GSKJ4 on NSCLC Cells Alone and in Combination with Metformin. (2016)
  • Author(s): Watarai et al.
  • Journal Title: Anticancer Research Volume: 36 Pages: 6083-6092
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] グリオーマ幹細胞 (2017)
  • Author(s): 北中 千史
  • Organizer: 第37回日本脳神経外科学会コングレス総会
  • Invited
• [Presentation] 悪性グリオーマの新規治療戦略 (2017)
  • Author(s): 北中 千史
  • Organizer: 第76回日本癌学会学術総会
  • Invited