Investigation of kinase signaling related to early drug tolerance to molecular-targeted drugs and development of therapies to overcome the tolerance

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20833
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Morimoto Kenji 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00768806)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 治療抵抗性 / 肺癌 / KRAS-G12C / AXL / YAP

Outline of Final Research Achievements

AXL signalling is involved in therapeutic resistance to KRAS-G12C inhibitors in AXL-high-expressing KRAS-G12C mutant lung cancer. In addition, AXL inhibitors were used to confirm their efficacy in combination with KRAS-G12C inhibitors. This study has revealed one of the molecular mechanisms involved in adaptive resistance to KRAS-G12C inhibitors. Early inhibition of AXL, which is involved in adaptive resistance, may increase the therapeutic efficacy of KRAS-G12C inhibitors and delay the time to resistance.

Free Research Field

肺癌の薬物療法

Academic Significance and Societal Importance of the Research Achievements

本研究により、AXL高発現の KRAS-G12C変異陽性肺がんでは、AXL阻害薬とKRAS-G12C阻害薬の初期からの併用治療が、がんの「初期治療抵抗性」を克服し、再発までの期間を大幅に伸ばせる有効な治療法であることが明らかになった。この治療法が実際の患者の治療へと発展することで、KRAS-G12C変異陽性肺がん患者の治療成績を向上させると同時に、肺がんの個別化医療」の推進に大きく貢献することが期待できる。