ArticleCancer research communications2025
Preclinical Activity of Datopotamab Deruxtecan (Dato-DXd), an Antibody-Drug Conjugate Targeting TROP2, in Poorly Differentiated Endometrial Carcinomas.
Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.Drug delivery · 2026Review
- Datopotamab deruxtecan in solid tumors: Recent research progress and clinical applications.Frontiers in oncology · 2026Review
- Research progress of antibody-drug conjugates in the treatment of endometrial cancer.Frontiers in oncology · 2026Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) targeting trophoblast antigen-2 (TROP2), a cell surface glycoprotein highly expressed in many epithelial tumors, to deliver DXd, a potent topoisomerase I inhibitor. We evaluated TROP2 expression in primary endometrial cancer cell lines and the activity of Dato-DXd against endometrial cancer cell lines with different TROP2 expression in vitro and in vivo. TROP2 expression was assessed in nine primary tumor cell lines by flow cytometry. Cell viability after exposure to Dato-DXd was evaluated using flow cytometry-based assays to calculate the IC50. Bystander effect assay assessed the viability of TROP2-negative cells when cocultured with high TROP2-expressing cells. Fluorescent anti-phosphorylated histone H2AX antibody was used to demonstrate double-strand DNA breaks. Antibody-dependent cell cytotoxicity was tested in vitro using 4-hour chromium release assays. In vivo activity of Dato-DXd was evaluated against TROP2-positive endometrial cancer xenografts. A total of 78% (seven of nine) of the primary endometrial cancer cell lines expressed TROP2. Endometrial cancer cell lines expressing TROP2 were significantly more sensitive to Dato-DXd compared with control ADC. Dato-DXd-exposed, TROP2-positive endometrial cancer demonstrated increased double-strand DNA breaks compared with non-binding conjugate exposure. Dato-DXd mediated antibody-dependent cell cytotoxicity against TROP2-positive cell lines and induced significant bystander killing of TROP2-negative tumors when admixed with TROP2-positive tumors. In vivo, injection of Dato-DXd was well tolerated and demonstrated impressive tumor growth inhibition against chemotherapy-resistant poorly differentiated endometrial cancer xenografts (P < 0.0001). In conclusion, Dato-DXd is a novel ADC with remarkable preclinical activity against poorly differentiated endometrial cancer cell lines overexpressing TROP2. Clinical trials with Dato-DXd in patients with recurrent endometrial cancer are warranted. SIGNIFICANCE: Targeted treatment of aggressive forms of endometrial cancer using the biomarker TROP2 is a significant opportunity for the development of treatments when patients are resistant to other lines of treatment. Here, we present data showing preclinical evidence of effectiveness of this biomarker-targeted therapy in endometrial cancer.
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