A novel vision for cancer treatment by a kinase activator

Research Project

Project/Area Number	16K18460
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Tumor therapeutics
Research Institution	Osaka Medical College
Principal Investigator	Tanaka Yoshihisa 大阪医科大学, 医学部, 助教 (20648703)
Research Collaborator	Hamaoka Hitomi
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	抗癌剤 / キナーゼ活性化剤 / キナーゼ活性化 / 癌細胞死 / 癌
Outline of Final Research Achievements	We identified novel small molecule compound CMB-236 during anticancer drug screening. Our studies found that 1) CMB-236 markedly induced elevation of kinase activity of a variety of tyrosine kinase receptors. 2) Cell death induced by CMB-236 was strongly dependent on caspase activity. 3) PI3K activated by CMB-236 treatment caused swelling of endosomes. Hence, we assumed that unusual activation of tyrosine kinase by small　molecule compound disturbed cell homeostasis resulting in induction of cell death.　In addition, in vivo studies showed that CMB-236 treatment in mice suppressed tumor growth. These findings suggested that such compounds can be considered as potential drug targets.
Academic Significance and Societal Importance of the Research Achievements	がんの多様性により臓器ごとではなく患者一人一人のがん細胞の特徴にマッチした抗がん剤を選択する時代が到来しつつある。抗癌剤の開発においてキナーゼ阻害剤が多く占めている中、キナーゼ活性化剤による抗癌活性はほとんど報告されていない。本研究において抗癌活性を持つキナーゼ活性化剤が同定された意義は大きく、新たな視点での創薬が期待され、抗癌剤としての選択の幅が広がると考えられる。