Development of a novel therapy targeting the stemness of esophageal cancer using organoid technology

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09205
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Haisa Minoru 川崎医科大学, 医学部, 教授 (70322229)
• Co-Investigator(Kenkyū-buntansha): 猶本 良夫 川崎医科大学, 医学部, 教授 (00237190) ; 深澤 拓也 川崎医科大学, 医学部, 准教授 (20379845) ; 山辻 知樹 川崎医科大学, 医学部, 教授 (40379730)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 食道癌 / オルガノイド / 癌幹細胞

Outline of Final Research Achievements

Recently, SOX2, a well-known lineage-specific oncogene in esophageal cancer, was required to maintain cancer stemness. CRISPR interference (CRISPRi) against SOX2, individually, failed to induce notable antitumor effects on patient-derived organoids of esophageal squamous cell carcinoma. Therefore, we generated CRISPRi against PIK3CA, which is amplified in squamous cell carcinoma and involved in carcinogenesis, and found that simultaneous inhibition of SOX2 and PIK3CA inhibited the growth of esophageal cancer organoids.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

世界では年間40万人が食道癌に罹患している。本研究は、食道扁平上皮癌における新しい抗腫瘍効果の誘導機序を提示しておりその学術的意義は大きい。食道癌オルガノイドライブラリの構築により、今後開発される治療薬の有効性や毒性評価など、癌ゲノム医療進展への波及効果も期待できる。