A novel vision for cancer treatment by a kinase activator

2018 Fiscal Year Final Research Report

• 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
• Keywords: 抗癌剤 / キナーゼ活性化剤

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.

Free Research Field

解剖学

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。