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Antibody-drug conjugates targeting DDR1 as a novel strategy for treatment of breast cancer

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机构: [1]West China-California Research Center for Predictive Intervention Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. [2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. [3]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. [4]Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
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关键词: targeted cancer therapy antibody-drug conjugate discoidin domain receptor 1 breast cancer

摘要:
Antibody-drug conjugates (ADCs) have emerged as a novel class of targeted cancer therapies and been successfully applied in the treatment of breast cancer (BC). Discoidin domain receptor 1 (DDR1) is a single transmembrane receptor tyrosine kinase and has been identified as a possible target for cancer. In this study, we explored the potential of an anti-DDR1 ADC, named T4H11-DM4, for the treatment of DDR1-positive BC. We demonstrated that high protein expression and RNA expression of DDR1 in BC tissues. In vitro, T4H11-DM4 was potently cytotoxic to DDR1-expressing BC cells, with IC50 in the nanomolar range. In mice BC xenograft models, T4H11-DM4 dramatically eliminated BC tumors, without observable toxicity. Taken together, our findings demonstrated that DDR1 can serve as a promising therapeutic target for BC.

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出版当年[2023]版:
大类 | 4 区 医学
小类 | 4 区 药学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 药学
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第一作者机构: [1]West China-California Research Center for Predictive Intervention Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
通讯作者:
通讯机构: [2]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China. [*1]West China Hospital, Sichuan University, Chengdu, #37 Guoxue Alley, Wuhou District, Chengdu, Sichuan Province, 610041, China
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