Possibility of antibody drug conjugate targeting EGFR in triple negative breast cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16780
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Juntendo University
• Principal Investigator: nakai katsuya 順天堂大学, 医学部, 准教授 (10384108)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 乳癌 / Triple Negative乳癌 / 上皮増殖因子受容体 / 抗体薬物複合体 / 効果予測因子 / アルギニン・メチルトランスフェラーゼ / メチル化

Outline of Final Research Achievements

The aim of this study was to analyze the methylation status of the extracellular domain of EGFR in triple negative breast cancer (TNBC) to identify the effect of antibody drug conjugate (ADC) and its predictive factors for the treatment of TNBC.　We analyzed the expression of EGFR and its methylation status in TNBC cell lines, and generated PRMT1-engineered cell lines (overexpression and knockdown models) to confirm the intracellular signaling changes. We used ADCs targeting EGFR in TNBC cell lines and confirmed the effect of the ADC. In addition, we confirmed the methylation status of EGFR in human TNBC samples, and confirmed the rate at which ADCs targeting EGFR are expected to be effective.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

ADCの登場により，TNBCに対する抗EGFR治療に新たな可能性が出てきている．ADC治療薬に関する治療予測因子についての検討はいまだ明白なものはない． ADCの治療効果予測因子としてEGFRのメチル化に注目し機能変化と薬剤耐性に関する報告はなく新規性および将来性があると考えられる．