Deep phenotyping of human colorectal cancer evolution using adult stem cell organoids and CRISPR-Cas9 technology

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03757
• 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: Keio University
• Principal Investigator: Fujii Masayuki 慶應義塾大学, 医学部(信濃町), 講師 (00867575)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん / オルガノイド / 浸潤 / 転移 / 遺伝子スクリーニング

Outline of Final Research Achievements

Colorectal cancer remains the main cause of cancer-related death in Japan, casting a substantive shadow on the society. This project investigated the progression of colorectal cancer with a particular focus on mechanisms of metastasis and drug resistance that define refractory and lethal cancer. Using the organoid culture system which enables expansion of somatic stem cells, we cultured patient-derived tumors and identified genes that facilitate liver metastasis via genetic screening. Using live-imaging of xenograft tumors, we further found that the awakening of dormant cancer stem cells contribute to tumor relapse after chemotherapy. Insights obtained from this research will contribute to deeper understanding of colorectal cancer biology and the future development of novel therapeutic strategies.

Free Research Field

がん生物学

Academic Significance and Societal Importance of the Research Achievements

がんは進行や治療に伴い、転移や治療抵抗性をはじめとした様々な能力を獲得し、最終的には致死的な病に至る。これらのメカニズムを理解することはがんの予後改善につながることが期待される一方で、その多くは未だ明らかになっていない。本研究では大腸がんをモデルとし、転移および抗がん剤耐性のメカニズムの一端を明らかにした。本研究で得られた知見は大腸がんの悪性化メカニズムの深い理解につながるとともに、今後の新規治療法の開拓の一助となることが期待される。