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2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20820
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto University
• Principal Investigator: Okamoto Takuya 京都大学, 医学研究科, 客員研究員 (20782915)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 大腸癌 / 腫瘍微小環境

Outline of Final Research Achievements

We analyzed the function of Osteoprotegerin (OPG) in the tumor microenvironment of colorectal cancer liver metastases. TCGA public database revealed a correlation between low OPG expression and poor prognosis in colorectal cancer. The analysis using immunohistochemistry of our colorectal cancer patients showed that liver metastasis was significantly frequent in the group with low OPG in primary colorectal cancer, and that OPG depletion in liver metastasis was observed in many patients with high OPG in primary colorectal cancer, suggesting that low OPG may be a cause of liver metastasis. We generated a mouse model of colorectal cancer liver metastasis and found that the low OPG-expressing cells were more prone to liver metastasis than the high OPG-expressing cells, and that the liver metastasis was suppressed by anti-RANKL antibody in the low OPG-expressing cells.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

日本人の半数が癌に罹患し、死亡の1/3が癌死と言われる時代において、癌の新規治療法の開発は社会的意義が大きい。しかし、新規抗がん剤開発には膨大な投資が必要となり、その結果新規抗がん剤は高価なものとなる。そのため既に臨床使用されている既存の薬剤の適応応用(drug repositioning)も、新規治療法開発の観点では重要となる。本研究では骨転移の治療薬として既に広く臨床使用されている抗RANKL抗体が大腸癌肝転移のなかでもOPG低発現大腸癌においては有効となる可能性が示された。