Development of new anti-angiogenic drugs for non-VEGF pathway using drug repositioning

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08944
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Okayama University
• Principal Investigator: Michiue Hiroyuki 岡山大学, 中性子医療研究センター, 准教授 (20572499)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 抗血管新生療法 / 抗血管背陰性薬 / 脳腫瘍幹細胞 / 膠芽腫 / VEGF / 既存薬再開発 / 血液脳関門 / 血管内皮細胞

Outline of Final Research Achievements

The current treatments for malignant brain tumors are mainly surgery, radiation therapy, and chemotherapy, and in addition to this, multidisciplinary treatment by combination therapy such as immunotherapy is performed, but the prognosis is previously poor.
Among them, the concept of anti-angiogenic therapy for malignant tumors has been advocated since the 1970s, and the development of bevacizumab, an anti-human VEGF monoclonal antibody, has been shown to be effective in colorectal cancer, ovarian cancer, lung cancer, etc. However, no prognosis-prolonging effect was observed in malignant tumors. This time, we have identified the cause of this treatment resistance and identified a new effect by using it in combination with a new drug.

Free Research Field

悪性脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍に栄養や酸素などを供給する腫瘍血管の形成をブロックして、腫瘍を兵糧攻めにする抗血管新生療法は、概念として素晴らしいものである。膠芽腫（悪性神経膠腫）に対する抗血管新生療法は、臨床試験において有効性を示さなかった。これはこの治療法の概念を否定するものでなく、使用したVEGFR/VEGF-R経路阻害薬の抗VEGF抗体だけでは不十分であるとの仮説を立て、本研究の着想に至った。我々は、治療抵抗性の原因となると考えた脳腫瘍幹細胞由来の新たな血管を攻撃する薬剤の開発研究を行った。またこの薬剤がどのような働きをするかを解明し、今後の研究発展へ繋げた。