Analysis of transcriptome in the tumor microenvironment to explore the pathogenesis and new treatment strategies of human pancreatic cancer.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08362
• 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: The University of Tokyo
• Principal Investigator: Hamada Tsuyoshi 東京大学, 医学部附属病院, 助教 (90723461)
• Co-Investigator(Kenkyū-buntansha): 立石 敬介 東京大学, 医学部附属病院, 講師 (20396948) ; 中井 陽介 東京大学, 医学部附属病院, 准教授 (80466755)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 膵癌 / ヒト

Outline of Final Research Achievements

The microenvironment of pancreatic cancer consists of tumor cells and a variety of cells in the surrounding stroma. In addition to this immunosuppressive tumor microenvironment, intratumor heterogeneity can lead to progression of tumor cells and treatment resistance. A better understanding of the dynamic network in the tumor microenvironment would help us to improve treatment strategies and prolong survival of patients with pancreatic cancer.
Utilizing a multi-institutional cohort of patients with pancreatic cancer, we have shown that KRAS variant allele frequency is inversely associated with recurrence-free and overall survival times. We now conduct gene expression analyses based on profiling of protein and RNA expressions. We will further integrate data on epidemiological factors (common medications, smoking, etc.) into our molecular database and aim to improve prognosis of pancreatic cancer patients through personalizing treatment strategies.

Free Research Field

膵癌の疫学

Academic Significance and Societal Importance of the Research Achievements

多施設での組織検体を用いて、膵癌発生に関連する主要な遺伝子変異であるKRAS変異を評価し、膵癌組織においてこの遺伝子変異をもつ細胞の割合が高いほど術後の再発率が高く、生存予後が不良であることを示した。この新たなバイオマーカー（予測因子）の発見により、より集学的な治療を要する膵癌患者の一群を同定し、今後の治療法開発や個別化治療への発展に寄与する結果を得た。現在、その他の因子（遺伝子の発現や、タンパク発現）の評価を進めており、さらに複合的なデータに基づいて膵癌患者の治療戦略をより良いものとすることを目指す。