Clarification of the mechanism of the tumor microenvironment related to treatment resistance to pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16458
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Juntendo University
• Principal Investigator: yu gyoda 順天堂大学, 医学部, 助教 (90838236)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵癌 / 癌内線維芽細胞 / 治療抵抗性

Outline of Final Research Achievements

In 15 of 24 cases of pancreatic cancer that had been surgically removed after preoperative chemotherapy, we successfully established CAFs from the cancerous area and control fibroblasts from the non-cancerous area. Immunohistochemical staining using antibodies specific to epithelial cells, mesenchymal cells, and blood cells confirmed that highly pure fibroblasts had been established. In addition, RNA-sequencing identified many genes whose expression was significantly increased in CAFs compared to control fibroblasts derived from non-cancerous areas. In the future, we plan to clarify whether CAFs contribute to anticancer drug resistance and the involvement of the identified genes in treatment resistance.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

膵癌は、抗癌剤治療中に高頻度に治療抵抗性を示す予後不良な癌である。この治療抵抗性に関して、癌間質に多く存在する癌内線維芽細胞(Carcinoma-associated fibroblasts : CAFs)の関与が示唆されているが、その分子機構については不明な点が多い。
CAFsと膵癌治療抵抗性の関係に関して、分子レベルで明らかにし治療に役立てられれば社会的意義は大きい。