A systematic approach to achieving glioblastoma cure via targeting glioma stem cells: PART2

• Project/Area Number: 15H04946
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Yamagata University
• Principal Investigator: KITANAKA CHIFUMI 山形大学, 医学部, 教授 (70260320)
• Research Collaborator: OKADA MASASHI
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: グリオブラストーマ / 神経膠芽腫

Outline of Final Research Achievements

In this project, to further advance to clinical application the achievements attained in our previous studies on glioma stem cells, we searched for drugs that can enhance the effect of metformin and, through the drug repurposing strategy, JNK inhibitors that are effective against cancer stem cells. As a result, we identified AS602801 and CEP-1347 as such JNK inhibitors with known safety profiles in humans. Moreover, we have unexpectedly succeeded in identifying a drug that has selective cytotoxicity against glioma stem cells.

Academic Significance and Societal Importance of the Research Achievements

がん（悪性新生物）は長年にわたり我が国の死亡原因圧倒的第１位を維持しており、がんの克服は国家的にも重要な課題である。本課題はがんの再発・転移の主要因と考えられているがん幹細胞に着目し、そのがん幹細胞に作用することで再発・転移を防ぎがん根治が期待できるがん幹細胞治療薬開発を目指そうとする課題である。本課題ではすでにヒトへの安全性が確認されている薬剤の中からがん幹細胞に有効な薬剤を見出し、しかもその効果を前臨床試験レベルで確認ずみであるなど、がん根治薬の臨床応用に向けて大きな一歩となりうる成果を挙げた。

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] The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. (2016)
  • Author(s): Okada M, Kuramoto K, Takeda H, Watarai H, Sakaki H, Seino S, Seino M, Suzuki S, Kitanaka C.
  • Journal Title: Oncotarget Volume: 19 Issue: 19 Pages: 27021-27032
  • DOI: 10.18632/oncotarget.8395
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] GSKJ4, a selective Jumonji H3K27 demethylase inhibitor, effectively targets ovarian cancer stem cells (2015)
  • Author(s): Sakaki et al.
  • Journal Title: Anticancer Research Volume: 35 Pages: 6607-6614
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] グリオーマ、固形がん幹細胞を標的とする治療法開発を目指したがん幹細胞研究 (2015)
  • Author(s): 北中 千史
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
  • Invited