Attempt to establish a novel therapeutic approach targeting long non-coding RNAs for EGFR-TKI-resistant lung cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08559
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Yamagata University
• Principal Investigator: SHO Ri 山形大学, 大学院医学系研究科, 助教 (80344787)
• Co-Investigator(Kenkyū-buntansha): 鈴木 潤 山形大学, 医学部, 助教 (70533925) ; 張 旭紅 山形大学, 大学院医学系研究科, 助教 (10292442) ; 濱田 顕 近畿大学, 大学病院, 助教 (80772954)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: lncRNA / 肺癌 / オルガノイド

Outline of Final Research Achievements

Acquired resistance remains a major obstacle to targeted therapies for non-small-cell lung cancer (NSCLC). This study aimed to investigate the potential of lncRNA S180122 inhibitors in overcoming drug resistance using patient-derived lung cancer organoids and cell line-derived spheroids. The results demonstrated that the inhibitor could attenuate EGFR-TKI resistance in resistant cell lines. However, no significant morphological or genetic changes were observed in organoids/spheroids, suggesting delivery challenges. Further optimization is needed to effectively deliver inhibitors to 3D tumor models for overcoming clinical drug resistance.

Free Research Field

腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

分子標的治療における耐性化機構の解明と克服薬の探索は、肺癌治療成績のさらなる向上につながる重要な課題である。本研究ではlncRNAを標的としたEGFR-TKI耐性肺癌に対する新規治療法の創出を目指したが、最終目標は達成できなかった。しかし、短期間で患者由来肺癌オルガノイドの作製方法を確立したことは、今後の肺癌創薬研究開発に貢献すると期待される。