2023 Fiscal Year Final Research Report
Elucidation of diversity and therapeutic target in scirrhous gastric cancer stroma
| Project/Area Number |
21KK0153
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安田 忠仁 公益財団法人がん研究会, がん研究所 発がん研究部, 客員研究員 (00867947)
内原 智幸 公益財団法人がん研究会, がん研究所 発がん研究部, 客員研究員 (60835172)
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| Project Period (FY) |
2021-10-07 – 2024-03-31
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| Keywords | シングルセル解析 / 胃がん / 間質 / CAFs / 多様性 |
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| Outline of Final Research Achievements |
Single-cell RNA sequencing analysis was performed to elucidate the diversity of gastric cancer stroma and identified three subgroups of tumor stroma. In addition, we found that platelet-derived growth factor (PDGF)-PDGF receptor (PDGFR) signaling (PDGF - PDGFR signaling) causes severe fibrosis in the scirrhous gastric cancer stroma, weakening the effect of immune checkpoint inhibitors. Furthermore, combination therapy with PDGFR inhibitor and immune checkpoint inhibitor was found to show a higher antitumor effect on fibrotic tumors such as scirrhous gastric and pancreatic cancers.
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| Free Research Field |
腫瘍生物学
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| Academic Significance and Societal Importance of the Research Achievements |
１細胞レベルでの遺伝子発現解析によって、癌の間質は組織には多様な細胞群が存在し、さらに各細胞群の中にもサブグループが存在していることが明らかになった。特にスキルス胃癌のような線維化が強い癌種では、Cancer associated fibroblasts (CAFs)と呼ばれる線維芽細胞が癌を促進する腫瘍間質で重要な働きをしており、今後の癌治療を考える際には、このサブグループの存在を踏まえた上で、治療戦略を立てることが重要である。
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