2023 Fiscal Year Final Research Report
Clinical application of the blood monitoring system in accordance with genomic information of circulating tumor cells
Project/Area Number |
21K08741
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Jichi Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
鈴木 浩一 自治医科大学, 医学部, 教授 (70332369)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | 血液モニタリング / ゲノムプロファイリング / 血中循環腫瘍細胞 / 循環腫瘍DNA / 切除不能胃癌 / HER2阻害薬 / 適応拡大 |
Outline of Final Research Achievements |
Despite success in the HER2 targeted therapies for metastatic gastric cancer patients, the conventional assessment of HER2 status in tumor tissue specimens is still under debate. In this study, significance of HER2 status on circulating tumor cells (CTCs) was elucidated. Thirteen patients with HER2 positive in tumor tissues (Group A) were treated with cytotoxic agents and HER2-targeted therapy while 14 patients were negative and treated with cytotoxic agents. In these 14 patients, 8 patients showed HER2 positive (Group B) and 6 patients displayed HER2 negative (Group C) on CTCs. HER2 expression was associated with EMT (p=0.024). Increased expression of EMT was seen in Group A and B. Group B showed worse PFS than others (7.0 M in B and 15.7 M in A plus C, p=0.008), suggesting Group B could be a candidate for expand indication of HER2 inhibitor. Monitoring of circulating tumor cells leads to the expand indication of the HER2 targeted therapies in patients with metastatic gastric cancer.
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Free Research Field |
消化器外科
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Academic Significance and Societal Importance of the Research Achievements |
我々は腫瘍のゲノムプロファイルがその進展・転移、治療の過程で変化する事に注目し、ゲノムプロファイルのモニタリングとその情報に基づく癌治療戦略の構築を進めてきた。循環腫瘍細胞(CTC)は極めて微量ではあるが、その情報量は多い。また、癌細胞そのものを抽出できるため、遺伝子異常のみならず蛋白発現の変化などの細胞変化を解析することが可能である。我々はマイクロ流路チップ内での繰り返しソーティング技術を用いる事で、高純度のCTCを分取することが可能となった。CTCを標的とした血液モニタリングシステムは循環腫瘍DNAの情報を補完し、組織パネルに変わる新たなプラットフォームとしてその実用化が期待される。
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