Basic research for AXL-targeted precision medicine

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08209
• 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: Wakayama Medical University
• Principal Investigator: Yamamoto Nobuyuki 和歌山県立医科大学, 医学部, 教授 (60298966)
• Co-Investigator(Kenkyū-buntansha): 洪 泰浩 和歌山県立医科大学, 医学部, 准教授 (80426519)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 分子標的治療 / 個別化医療 / 肺癌

Outline of Final Research Achievements

Preclinical evaluation of micro-fluicid cell sorter for detecting CTCs was conducted and sensitivity of 61% in detecting rare tumor cells was confirmed. Detection rate overtime using the preserve tube was also evaluated and 60% or more sensitivity was confirmed. Additional immuno-staning for AXL is being tested for the clinical evaluation. Next-generation sequencing using rae tumor cells were evaluated and DNA extracted from 10 or more cells were sufficient for the sequencing. Organod culture using small tissue specimens were tested and it was confirmed to be technically feasible and detection of somatic mutations using those organoids was also feasible. Organoid culture using CTCs are now ongoing.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

CTCの臨床的意義については数多くの報告があるが、AXL発現陽性CTCのゲノム及び分子生物学的特徴の解明は十分になされていない。これらを明らかにすることで、肺がんにおけるリキッドバイオプシーとしての新たな診断法確立や新規の治療戦略、そして創薬につながる可能性がある。本研究開発においてはAXL陽性CTCの機能、臨床意義のより詳細な研究のため、CTC由来オルガノイド細胞株の樹立に取り組んだ。従来は明らかでなかったAXL陽性CTCの特徴を分子生物学的レベルで解明することにつながるとともに、創薬ツールとして利用することで、CTCを利用した診断法、治療戦略及び薬剤開発への橋渡しとなる可能性がある。