Precision medicine using circulating tumor cells of gastrointestinal cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Shoji Hirokazu 国立研究開発法人国立がん研究センター, 中央病院, 医員 (50765568)
• Co-Investigator(Kenkyū-buntansha): 本田 一文 国立研究開発法人国立がん研究センター, 研究所, 部門長 (10260936)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 末梢循環腫瘍細胞 / 胃癌 / tumor mutation burden / nivolumab

Outline of Final Research Achievements

Circulating tumor cells (CTCs) could be isolated from peripheral blood of a total of 11 patients with advanced gastric cancer, prior to the start of nivolumab in the third line of therapy. Next-generation sequencing was performed from the amplified DNA, and oncogenes and cancer-promoting gene mutation profiles were successfully extracted from CTCs. The gene mutation profiles of CTCs and ctDNA from surgical specimens (FFPE) and liquid biopsy specimens obtained from the same patient were different. Therefore, the combined use of both CTCs and ctDNA profiles was expected to improve gene mutation detection compared to each assay alone; the TMBs of FFPE and CTCs were not consistent, and the TMB of CTCs tended to be lower than that of FFPE.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

CTCs から消化管がんの「がんの個性診断法」を実現できれば、患者に対して最少侵襲で時々刻々変化するがん細胞に対して「適時・最適医療」を提示できるようになると考え、本研究を進めてきた。本研究の結果、進行胃がんCTCsからの遺伝子変異解析、TMB解析が可能でることを証明した。今後は本技術を用いて検討症例数を増やし、そして臨床試験への応用、CTCsの細胞培養が実現できれば、プロテオーム解析や薬剤感受性試験につながり、個々の患者に適した薬剤の提供につながる可能性があり、国内外へのインパクトが非常に高いと考える。