Therapeutic strategy against gastrointestinal cancer by utilizing cancer hierarchy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04157
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Seno Hiroshi 京都大学, 医学研究科, 教授 (90335266)
• Co-Investigator(Kenkyū-buntansha): 福田 晃久 京都大学, 医学研究科, 講師 (70644897)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸癌 / 膵臓癌 / 可塑性 / 分化

Outline of Final Research Achievements

During cancer development, cancer stem cells are closely associated with hierarchy and plasticity of cancer tissues. Previously, we reported that Dclk1 is one of the cancer stem cell-specific markers, and that SWI/SNF complex regulates differentiation of gastrointestinal cancers. Based on these findings, we here investigated (1) therapeutic strategy by utilizing cancer hierarchy and cancer stem cells, (2) therapeutic strategy by focusing on plasticity and differentiation status, and (3) detrermined them in organoid and patient-derived xenograft systems. These experiments indicated fundamental data to develop novel therapeutic strategies against various gastrointestinal cancers.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて、正常組織への傷害を回避しつつ癌組織を選択的に退縮させる理想的な癌治療へ近づくための基礎的知見を得ることができた。また、可塑性を応用した分化誘導治療に道を拓き、臓器の違いを超えた消化器癌治療の開発につながる将来性が期待される。このように、消化器癌の階層性と可塑性の本態に迫ろうとする学術的側面と、ヒト消化器癌の生体外可視化モデルを併用して「消化器癌幹細胞標的・分化誘導治療法開発」へ向けた創薬標的を検証する臨床的側面の双方で意義を有する研究と思われた。