2023 Fiscal Year Final Research Report
Developing a novel treatment strategy by elucidating the pathogenesis of cancer cachexia
| Project/Area Number |
22K19462
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原田 結花 地方独立行政法人東京都立病院機構東京都立駒込病院(臨床研究室), 臨床試験科, 部長 (50379848)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Keywords | がん悪液質 / 悪性腫瘍 / 血液がん / 創薬 / 筋委縮 |
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| Outline of Final Research Achievements |
Most patients with advanced cancer develop cachexia, a multifactorial syndrome characterized by progressive skeletal muscle wasting. Despite its catastrophic impact on survival, the critical mediators responsible for cancer cachexia development remain poorly defined. We show that a distinct subset of neutrophil-like monocytes, which we term cachexia-inducible monocytes (CiMs), emerges in the advanced cancer milieu and promotes skeletal muscle loss. Transcriptome analysis revealed that IL36G-producing CiMs are induced in chronic monocytic blood cancer characterized by prominent cachexia. The emergence of CiMs were also confirmed in various advanced solid cancers. Stimuli of TLR4 signaling were responsible for the induction of CiMs. Genetic inhibition of IL36G-mediated signaling attenuated skeletal muscle loss and rescued cachexia phenotypes in advanced cancer models. These findings indicate that CiMs could be a potential therapeutic target in cancer cachexia.
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| Free Research Field |
医学、血液内科、腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
がん悪液質は、通常の栄養サポートでは完全に回復することができず、進行性の機能障害に至る、脂肪量減少の有無を問わない骨格筋量の持続的な減少を特徴とする多因子性の症候群である。進行がん患者の50～80％で認められ、約20％のがん死亡への間接的関与が示唆されている。全身性の炎症や代謝異常との関連性が指摘されているが、病態発症の詳細な機序は不明である。現状の治療法として確立したものはなく、期待された食欲不振に対する食欲促進薬による治療効果は限定的である。本研究の成果は、死因第一位のがんにおけるアンメット・メディカル・ニーズである悪液質の新規治療法に繋がるものである。
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