Development of Molecularly-Targeted Anticancer Drug Susceptibility Tests Using Oral Cancer Secretory Exosomes

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10288
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Okayama University
• Principal Investigator: Murakami Jun 岡山大学, 歯学部, 博士研究員 (40362983)
• Co-Investigator(Kenkyū-buntansha): 長塚 仁 岡山大学, 医歯薬学域, 教授 (70237535) ; 河合 穂高 岡山大学, 医歯薬学域, 助教 (10803687) ; 高畠 清文 岡山大学, 医歯薬学域, 助教 (70736537)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 口腔扁平上皮癌 / エクソソーム

Outline of Final Research Achievements

Oral cancer cells increased the release of extracellular vesicles upon EGF stimulation, and these extracellular vesicles expressed high levels of EGFR. This suggests the involvement of extracellular vesicles in the metabolism of cetuximab, an anti-EGFR antibody drug. When oral cancer cells were treated with cetuximab, cetuximab was detected in the cell and extracellular vesicle fractions.
This suggests that cetuximab targets extracellular vesicles by binding to EGFR in these vesicles. When cetuximab was applied to EGFR-highly expressing extracellular vesicles released by oral cancer cells, uptake by macrophages and normal epithelial cells was reduced. This suggests that cetuximab may exert its antitumor effect by inhibiting the uptake of extracellular vesicles into the tissues surrounding the cancer.

Free Research Field

歯科放射線

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、口腔癌細胞が分泌する細胞外小胞を介したセツキシマブ耐性機序の一部が明らかとなった。この成果により、新たな薬剤耐性機構に則した治療の開発や、化学療法患者の血中のエクソソーム中の薬剤の分量を定量することで、患者の新たな薬剤感受性試験を開発することが可能となる。