New therapeutic strategy for cancer cachexia induced cardiac dysfunction

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21645
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology; Applied pharmacology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Nonaka Miki 国立研究開発法人国立がん研究センター, 研究所, 特任研究員 (60758077)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: がん悪液質 / Cardio-oncology

Outline of Final Research Achievements

We established a novel murine model of cancer cachexia by implantation of human stomach cancer cell line 85As2 presenting anorexia, weight loss and low fat-free mass similar to those observed in patients. By using this model, we evaluated the effect of cachexia on cardiac function. At 2 weeks after implantation (pre-cachexia group), the mice began to show symptomatic cachexia; decreased body, skeletal muscle, and heart weight. The cachexia group (at 8 weeks after inoculation) developed severe cardiac atrophy in heart weight compared to controls. In addition, left ventricular ejection fraction was significantly decreased in pre-cachexia and cachexia group compared with age-matched controls. Histological and biochemical analyzes suggest that cardiac dysfunction may be caused by a pathway different from that of skeletal muscle atrophy. Further study is considered to be needed.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

がんサバイバーの増加とともに、今まで顕在化していなかったがんサバイバーのQOLと心疾患についての関連性が近年指摘されている。がんサバイバーのフォローアップも含めた循環器系動態の把握、ならびにがん治療の有効性とがん治療に伴って起こる心機能障害を予防するために腫瘍循環器学という新しい学際領域が誕生した。本研究課題はこの腫瘍循環器学領域での研究の先駆けとなるものであり、がん悪液質によって心機能障害が起こること、さらにそのメカニズムの一端を明らかにすることができた。今後はがん悪液質で起こる心機能障害に対する予防薬や治療法についても詳細な検討を行っていきたいと考えている。