Strategies to prevent progression from premalignant lesion to cancer in the pancreas

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19480
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Seno Hiroshi 京都大学, 医学研究科, 教授 (90335266)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 膵がん

Outline of Final Research Achievements

To improve preventive and therapeutic efficacy against pancreatic cancer, it would be important to analyze the early steps of pancreatic cancer development. In this project, we analyzed the early steps of pancreatic carcinogenesis; ADM (acinar-to-ductal metaplasia) formation and Kras activation. By using lineage tracing technique and RNA expression analyses, we performed following experiments. 1) In vivo lineage tracing in ADM, 2) Extraction of key signaling cascades during de-differentiation and re-differentiation of ADM, 3) Determinants to promote the transition from ADM to pancreatic tumor. Through these experiments, we could approach the core mechanisms of the early steps of pancreatic carcinogenesis, and at the same time obtain several hints to prevent the progression from ADM to pancreatic cancer progenitors.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究はADMという膵臓のユニークな病変を手がかりに実験を展開するもので、他臓器のがん研究には見られない独自性を有するとともに、生体が持つ可塑性にチャレンジする試みであった。また、CreERにより任意のタイミングでADMにKras変異を挿入して膵腫瘍を形成させる実験系、過去困難であったADMの動態を生体内で経時的に可視化する実験系など、申請者らが構築してきたシステムが有用であった。そこに先端的な遺伝子解析技術を併用して、膵発がんの超初期病変の本質に挑む解析は、他では実施困難な挑戦的内容と思われた。さらにそこから得た知見を、中長期的に新規膵がん予防、治療法へ発展させる萌芽とすることができた。