Development of novel treatment of HER2-positive breast cancer by inhibiting vasculagenic mimicry

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Osaka University
• Principal Investigator: Shimoda Masafumi 大阪大学, 大学院医学系研究科, 准教授 (30644455)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: vascular mimicry / vessel co-option

Outline of Final Research Achievements

High-grade breast cancer, which has a strong ability to proliferate and easily metastasize, tries to survive by altering its characteristics. It is known that it attempts to acquire blood flow by transforming into a similar nature as the endothelium that forms the walls of blood vessels, but there are currently no treatment drugs available to suppress this phenomenon. The applicant has discovered in previous research that this phenomenon can be suppressed by inhibiting cell movement. In this study, we discovered that a small molecule compound called Defactinib, which targets cell movement, prevents breast cancer cells from moving and forming blood vessel-like structures. Additionally, in a mouse breast cancer model, we found that Defactinib reduces tumor blood vessels and inhibits tumor growth.

Free Research Field

乳腺外科学

Academic Significance and Societal Importance of the Research Achievements

HER2陽性乳癌やトリプルネガティブ乳癌という悪性度の高い乳癌は全体の3分の1程度を占め、その再発率の高さや再発後の生存期間の短さが問題である。本研究では悪性度の高い乳癌が持つ可塑性に着目してその性質を阻害する薬剤を見出すことにした。腫瘍の増大には血流の獲得が必要だが、乳癌細胞自身が血管内皮様の性質を持つことがある。本研究で申請者はデファクチニブという低分子薬剤が乳癌細胞を動きにくくして血管様の構造をとることを阻害し、腫瘍の増大を抑制することを初めて見出した。これは乳癌治療における新たな治療法となる可能性を持つ。本研究の更なる発展により、乳癌の治療成績の向上が図られることが期待される。