Development of novel therapy targeting tumor-elicited inflammation in colorectal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03758
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hokkaido University
• Principal Investigator: Taniguchi Koji 北海道大学, 医学研究院, 教授 (20627020)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん / 炎症 / 組織再生

Outline of Final Research Achievements

It is known that chronic inflammation contributes to invasion and metastasis of many cancers, but the detailed mechanism is still unknown. To artificially control anti-tumor immunity, it is important to clarify the molecules and cell types that regulate chronic inflammation in the tumor microenvironment. In this study, we examined how driver gene mutations and inflammatory regenerative signals regulate production of cytokines, chemokines and growth factors produced by cancer cells and how these molecules affect chronic inflammation and anti-tumor immunity in the tumor microenvironment by using new technologies such as organoid culture, CRISPR/Cas9 system, and comprehensive analysis. For that purpose, we have established genetically modified organoids, which were mutated with oncogenes and tumor suppressor genes that are important in the multi-stage carcinogenesis hypothesis of colorectal cancer, and analyzed gene expression of these organoids.

Free Research Field

がん

Academic Significance and Societal Importance of the Research Achievements

今回は新規技術である腸オルガノイド培養や網羅解析、CRISPR/Cas9によるゲノム編集などを用いて、がん細胞自身のドライバー遺伝子変異やそれに伴う炎症（新規炎症シグナル伝達経路Src-YAP経路やJAK-STAT3経路）がどのようにがん免疫に影響を与えるかという新しい観点から研究を行っており、新規がん治療方法の開発に繋がることが期待される。