Novel therapeutic strategy against colorectal cancer by intervening fluctuated differentiation status

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03659
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kyoto University
• Principal Investigator: Seno Hiroshi 京都大学, 医学研究科, 教授 (90335266)
• Co-Investigator(Kenkyū-buntansha): 中西 祐貴 京都大学, 医学研究科, 特定助教 (40838679)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸がん

Outline of Final Research Achievements

Cancer heterogeneity and plasticity are major causes of resistance against anti-cancer therapy. One of the reasons for those phenomena is fluctuation of cancer/cancer stem cell differentiation status. In this study, we performed comprehensive analyses for factors that affect fluctuation of differentiation status and stemness of colorectal cancer, and examined underlying mechanisms during those processes. We extracted a subtype of colorectal cancers that is associated cancer stemness phenotype, identified several factors that affect fluctuation of cancer differentiation status and cancer stemness, and showed potential effectiveness of intervening those newly identified factors.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では大腸を舞台に、がん細胞に分化の揺らぎと幹細胞性をもたらすメカニズムの解析、分化の揺らぎとがん幹細胞を標的とするがん治療法開発へ向けた基盤的データ獲得を目的とした。マテリアルとなった種々の遺伝子改変マウス、マウスおよびヒト由来オルガノイド、腫瘍/がん幹細胞マーカー、経時的観察を可能にするライブ・イメージング系、および腫瘍/がん幹細胞の選択的排除システムは、研究代表者らが独自に検証、樹立してきたもので、本研究のオリジナリティは高い。がん幹細胞とその揺らぎは、大腸がんのほか、膵臓がん、胃がん、胆道がん等にも存在し、将来的に臓器横断的な消化器がんの治療法開発につながる可能性も考えられる。