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

Authors :
Tao Y
Lu Y
Xue T
Lai Q
Song H
Chen X
Guo C
Yang J
Wang Y
Source :
Journal of drug targeting [J Drug Target] 2024 Dec; Vol. 32 (10), pp. 1295-1304. Date of Electronic Publication: 2024 Aug 09.
Publication Year :
2024

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 T <subscript>4</subscript> H <subscript>11</subscript> -DM4, for the treatment of DDR1-positive BC. We demonstrated that high protein expression and RNA expression of DDR1 in BC tissues. In vitro , T <subscript>4</subscript> H <subscript>11</subscript> -DM4 was potently cytotoxic to DDR1-expressing BC cells, with IC50 in the nanomolar range. In mice BC xenograft models, T <subscript>4</subscript> H <subscript>11</subscript> -DM4 dramatically eliminated BC tumours, without observable toxicity. Taken together, our findings demonstrated that DDR1 can serve as a promising therapeutic target for BC.

Details

Language :
English
ISSN :
1029-2330
Volume :
32
Issue :
10
Database :
MEDLINE
Journal :
Journal of drug targeting
Publication Type :
Academic Journal
Accession number :
39072640
Full Text :
https://doi.org/10.1080/1061186X.2024.2386621