Development of therapies for small cell lung cancer based on regulating macrophage activation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08603
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: Iriki Toyohisa 熊本大学, 大学院生命科学研究部(医), 特定研究員 (20802078)
• Co-Investigator(Kenkyū-buntansha): 藤原 章雄 熊本大学, 大学院生命科学研究部(医), 講師 (70452886) ; 一安 秀範 熊本大学, 大学院生命科学研究部(医), 准教授 (50419636)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 小細胞肺癌 / 腫瘍関連マクロファージ

Outline of Final Research Achievements

To develop a novel therapeutic strategy for small cell lung cancer, we examined the effect of a therapeutic strategy using compounds regulating the activation of tumor-infiltrating macrophages on small cell lung cancer progression. In the present study, we demonstrated that Onionin A, a cyclic sulfur compound, and its derivatives inhibit tumor proliferation by regulating macrophage activation through suppressing STAT3 activation. Those compounds also suppressed tumor progression in small cell lung cancer-bearing mice by stimulating tumor immunity through regulating the activation of tumor-infiltrating macrophages. Therefore, it is suggested that the regulating macrophage activation may be a candidate for a novel therapeutic strategy against small cell lung cancer.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は標準治療の進歩に乏しい小細胞肺癌に対して、マクロファージの活性化を調節する化合物を治療に応用しようとする研究であり、本研究にて数種の環状スルフィド化合物がマクロファージの活性化制御により小細胞肺癌に有効性を示すことを明らかにした。本研究成果は小細胞肺癌治療において腫瘍微小環境の制御が治療ターゲットとなりうる可能性を明らかにしたことで新たな治療戦略の一助となるものと考えられる。