Elucidation of Tumor Heterogeneity and Treatment Resistance Mechanisms Using PDX Model Library of Colorectal Cancer Metastases

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16360
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyushu University
• Principal Investigator: NAGAYOSHI Kinuko 九州大学, 大学病院, 助教 (90761015)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 大腸癌 / 肝転移 / 腫瘍不均一性 / PDXモデル

Outline of Final Research Achievements

Single-cell RNA library generation was performed on surgical specimens from several types of solid tumors, including gastric, esophageal, and colorectal cancer, and analyzed by NGS. We have now succeeded in stably generating enough single cell suspensions and have generated libraries for more than 50 human solid tumors. The data after NGS analysis are analyzed using the R package Seurat, focusing on the characteristics and functions of the cell population, pseudo-genealogical analysis to determine the direction of cell differentiation, and analysis of cell-cell interactions.
In addition, our laboratory has already created a PDX model of pancreatic cancer and has attempted to create a PDX model using primary colon cancers and metastases but has not yet been able to establish one.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

原発巣・転移巣間、細胞集団間、機能的なheterogeneityを明らかにすることで、転移・再発・治療抵抗性の機序を細胞レベルで明確にすることができる。また、PDXモデルを用いることで化学療法感受性や抵抗性獲得と関連する細胞集団ごとの遺伝子発現パターンを経時的に解析することができれば、細胞の進化や選択的生存の機序解明につながり、学術的にも重要な知見となる。さらに、これらの知見が新たな転移性大腸癌の治療開発につながれば、学術や科学技術の面だけでなく多くの癌患者を含めた医療社会へ大きく貢献することとなる。