Development of novel molecular targeted therapy for pancreatic cancer with Notch / Sox9 signal inhibitor

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K18439
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Chiba University
• Principal Investigator: Kagawa Shingo 千葉大学, 医学部附属病院, 助教 (90507302)
• Research Collaborator: Higashihara Taku 千葉大学, 大学院医学研究院
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 膵臓癌 / Sox9 / 癌幹細胞

Outline of Final Research Achievements

Pancreatic cancer is aggressive disease and in many patients it recur even after curative resection. It is also known that it will become chemo-resistance after treatment. We focused on the transcription factor Sox9, which is thought to regulate differentiation at the developmental stage of the pancreas, and found that the intensity of Sox9 expression was associated with the prognosis after surgery. We analyzed the characteristics of pancreatic cancer cell line and showed the strength of Sox 9 is associated with chemo resistance and such cells have cancer stem cell properties. Furthermore, in a mouse subcutaneous tumor model, Sox9 was associated with tumorigenicity, indicating that Sox9 could be a target for treatment of pancreatic cancer.

Free Research Field

膵臓癌

Academic Significance and Societal Importance of the Research Achievements

癌の悪性度や治療抵抗性を特徴とする癌幹細胞の概念に近年注目が集まっており、このような癌幹細胞を治療標的とすることが必要と考えられている。一方、このような癌幹細胞を生体内で特徴づけるマーカーを見出すことや、如何にこのような細胞を除去するかは、膵癌を克服するための重要な課題である。今回我々は、Sox9が膵癌幹細胞の維持に貢献しており、治療対象となり得ることを示した。未だSox9をターゲットとした治療方法の開発は研究段階であるが、難治性癌である膵臓癌治療への糸口を示すことができたと考える