Establishment of single-cell organoid culture system and elucidation of drug resistance mechanisms.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07209
• 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: Kanagawa Cancer Center Research Institute
• Principal Investigator: Hoshino Daisuke 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 部門長 (30571434)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オルガノイド / 薬剤耐性

Outline of Final Research Achievements

Intratumor heterogeneity (ITH) is one of the factors that make cancer treatment difficult. Although pathological and genetic analyses using clinical specimens have deepened our understanding of ITH, few studies have explored its biological characteristics. One of the reasons for this is the lack of cultured cell lines that retain the same level of ITH as tumor tissue. In this study, we first established single-cell organoid culture lines based on organoid culture lines derived from patients with intractable cancer that we established. Next, we performed genetic and pathological analyses and comprehensive signal transduction variation analyses using the established organoid culture lines and the originally preserved tissues before and after anticancer drug administration.

Free Research Field

がん生物

Academic Significance and Societal Importance of the Research Achievements

これまでに、切除検体と同程度に腫瘍内不均一性を維持できている培養細胞株はない。本研究では、これまでに申請者が樹立した難治がん患者由来PDOから、シングルセルPDOを樹立し、それらを用いて腫瘍内不均一性に基づいた薬剤耐性機構の解明を目的とした。これまでにシングルセル PDO 樹立の報告はなく、独自性の高い研究であるといえ、そこから得られた研究結果は学術的意義が高く、将来的に臨床応用できれば社会的意義も高いと思われる。