Stratification and optimization of pancreatic cancer treatment based on chromatin dynamics

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15966
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kato Hiroyuki 東京大学, 医学部附属病院, 特任臨床医 (70829788)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 膵管内乳頭粘液性腫瘍(IPMN) / 膵臓癌 / オルガノイド / 次世代シーケンサー / クロマチン / エピゲノム / ゲノム構造

Outline of Final Research Achievements

Unraveling the pathogenesis of various pancreatic tumors is an urgent issue for their treatment optimization. Among them, intraductal papillary mucinous tumor (IPMN) is one of the precursor lesions in pancreatic cancers, which is often identified as a pancreatic cyst in health checkups. Although the number of patients with IPMN is increasing, no treatment has been established to prevent IPMN carcinogenesis other than surgical resection. Therefore, understanding of the tumor progression process of IPMN has been warranted.
To achieve this, we have established a series of original patient derived IPMN organoids. By applying cutting-edge genomic and epigenomic analyses to these models, we have identified that IPMN have distinct epigenomic profiles with characteristic addictive behaviors supported by MNX1-HNF1B axis, implying a feasibility for therapeutic implementation in this disease. These findings may contribute to the control of IPMN pathogenesis.

Free Research Field

膵臓癌

Academic Significance and Societal Importance of the Research Achievements

我々はIPMN の多様な消化器臓器系譜を模して進展する臨床病理学的特徴に着目し、細胞系譜を司るエピゲノムにこそ、その本質が潜在すると仮説立てることで疾患の本質を追求するに至った。臨床に則した視点と、患者検体の有効活用、先端技術の融和による病態解明手法の有用性を提唱するとともに、蓄積したオミクスデータはIPMN の悪性化過程の解明、並びに新規治療標的を探索する重要な資源になると考える。
加えて、本研究を足掛かりに前癌段階のIPMN時点での腫瘍の脆弱性を検討することの重要性や、発癌予防へ向けたIPMN診療のパラダイムシフトを提案する一助となればと考える。