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针对 DDR1 的抗体药物偶联物作为治疗乳腺癌的新策略。

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

机构信息

West China-California Research Center for Predictive Intervention Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

J Drug Target. 2024 Dec;32(10):1295-1304. doi: 10.1080/1061186X.2024.2386621. Epub 2024 Aug 9.

Abstract

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 TH-DM4, for the treatment of DDR1-positive BC. We demonstrated that high protein expression and RNA expression of DDR1 in BC tissues. , TH-DM4 was potently cytotoxic to DDR1-expressing BC cells, with IC50 in the nanomolar range. In mice BC xenograft models, TH-DM4 dramatically eliminated BC tumours, without observable toxicity. Taken together, our findings demonstrated that DDR1 can serve as a promising therapeutic target for BC.

摘要

抗体药物偶联物 (ADC) 已成为一类新型的靶向癌症治疗药物,并已成功应用于乳腺癌 (BC) 的治疗。盘状结构域受体 1 (DDR1) 是一种单一的跨膜受体酪氨酸激酶,已被确定为癌症的潜在靶点。在这项研究中,我们探索了抗 DDR1 ADC 药物 TH-DM4 治疗 DDR1 阳性 BC 的潜力。我们证明了 DDR1 在 BC 组织中的高蛋白表达和 RNA 表达。TH-DM4 对表达 DDR1 的 BC 细胞具有强大的细胞毒性,IC50 值在纳摩尔范围内。在小鼠 BC 异种移植模型中,TH-DM4 显著消除了 BC 肿瘤,没有观察到毒性。总之,我们的研究结果表明,DDR1 可以作为 BC 的一个有前途的治疗靶点。

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