Elucidating the pathophysiology of cancer cachexia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Kojima Yasushi 愛知県がんセンター(研究所), がん病態生理学分野, 主任研究員 (30464217)
• Co-Investigator(Kenkyū-buntansha): 三城 恵美 (佐藤恵美) 名古屋大学, ITbM, 特任講師 (00455544)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん悪液質 / ビタミンB / NAD

Outline of Final Research Achievements

Cancer cachexia is characterized by significant weight loss, reduced appetite, and muscle wasting. The underlying mechanisms of cancer cachexia are not yet fully understood, and there is currently no effective treatment. In studies involving mouse models of cancer cachexia, we observed that NAD (nicotinamide adenine dinucleotide) levels were reduced by about 50%, and the expression of CD38, an enzyme that degrades NAD, was significantly increased. Vitamin B cocktails containing NAD precursors did not prolong survival in the SEKI cancer cachexia mouse models. Administrating compound 78c, a CD38 inhibitor, increased their liver and skeletal muscle mass. Additionally, we observed a decrease in blood levels of tryptophan, a precursor for NAD, in both mice with cancer cachexia and patients with gastric cancer cachexia. These findings provide crucial insights into the metabolic disturbances associated with cancer cachexia and could guide the development of future therapies.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がん悪液質は、進行性の体重減少・骨格筋萎縮・食思不振を主徴とする複合的な代謝性症候群である。多くの進行がん患者が、悪液質を発症し、がん悪液質はがん患者の約20％にとって直接死因であるとされる。紀元前の文献にも、悪液質に関する記録が残されているが、現在に至るまで、悪液質の本態は不明である。がん悪液質の本態は依然として不明で、実効性のある早期診断方法や治療介入法の開発が望まれている。本研究成果はがん悪液質の代謝学的側面の解明に関して一定の貢献をすることが期待される。