Elucidation of therapeutic resistance mechanisms associated with microenvironmental alteration using organoid and single cell analysis of colorectal cancer liver metastases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07677
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyushu University
• Principal Investigator: FUJITA Hayato 九州大学, 医学研究院, 共同研究員 (40611281)
• Co-Investigator(Kenkyū-buntansha): 水元 一博 国際医療福祉大学, 赤坂心理・医療福祉マネジメント学部, 教授 (90253418) ; 池永 直樹 九州大学, 大学病院, 助教 (90759755)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / 肝転移 / オルガノイド / scRNA-seq

Outline of Final Research Achievements

Organoid of colon cancer liver metastases has not yet been established. We have prepared cDNA libraries for scRNA-seq of more than 100 cases of gastrointestinal cancers including colorectal cancers. For colorectal cancer, we clarified heterogeneity of various immune cells and fibroblasts, performed pseudotime analysis to understand the flow of differentiation of the obtained subpopulations. We also analyzed cell-cell interactions. We clarified changes in the immune microenvironment during colorectal carcinogenesis. Furthermore, we analyzed the effects of preoperative chemotherapy for the microenvironment of esophageal squamous cell carcinoma.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本邦における大腸癌罹患率および死亡率は年々増加傾向にあり、切除後の補助化学療法を行っても再発する例や、再発後に切除を目指し化学療法を行っても制御困難となり致死的経過を辿る例は依然として多く、その素因として肝転移腫瘍の化学療法への抵抗性獲得があげられる。そのため、大腸癌転移性肝腫瘍の化学療法抵抗機序の解明は、それを打破する新規治療法や個別化治療の開発において社会的要求度・貢献度が非常に高い。