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2019 Fiscal Year Final Research Report

Investigation for a mechanism of cetuxifmab resistance in head and neck cancers

Research Project

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Project/Area Number 17K07203
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionKindai University

Principal Investigator

YONESAKA Kimio  近畿大学, 医学部, 講師 (30330260)

Co-Investigator(Kenkyū-buntansha) 坂井 和子  近畿大学, 医学部, 講師 (20580559)
土井 勝美  近畿大学, 医学部, 教授 (40243224)
北野 睦三  近畿大学, 医学部, 講師 (60716330)
田中 薫  近畿大学, 医学部, 講師 (80548628)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywords薬効評価と予測 / HER3 / ヘレグリン / アファチニブ
Outline of Final Research Achievements

The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is standard therapy for head and neck squamous cell carcinoma (HNSCC), whereas the underlying mechanisms for resistance to it has been unknown. The current study reveals that HER3 ligand heregulin causes the resistance to cetuximab in HNSCC. Heregulin knockdown with siRNA recovered the sensitivity to cetuximab in the cetuximab-resistant HNSCC FaDuCR cells. Furthermore pan-HER inhibitor afatinib could decrease HER3 activation and overcome the resistance to cetuximab in FaDuCR xenografted mouse model study. Finally, two among 28 tumors of HNSCC aberrantly expressed heregulin and those were resistant to cetuximab-based therapy.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

EGFR阻害剤は頭頚部癌のみならず非小細胞肺癌、大腸癌などで有効性が確立されている。そしてEGFR遺伝子の2次変異やHER2遺伝子増幅などが同剤の耐性化をもたらす。しかし頭頚部癌では未だセツキシマブの耐性機序が不明であったため、今回HER3リガンドであるヘレグリン依存的な耐性が明らかとなったことは学術的な意義がある。またHER3の阻害剤がセツキシマブ耐性頭頚部癌において有益である可能性が示唆された。この点は今後の進行期頭頚部癌の予後の改善につなげる上で重要と考える。

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Published: 2021-02-19  

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