ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Antitumor Activity and Biomarker Analysis for TROP2 Antibody-Drug Conjugate Datopotamab Deruxtecan in Patient-Derived Breast Cancer Xenograft Models.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- FDA Approval Summary: Datopotamab Deruxtecan-dlnk for Treatment of Patients with Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Antibody-drug conjugates in breast cancer: redefining targeted therapy.The Journal of clinical investigation · 2026Review
- Pan-cancer multi-omic integration of Trop2 reveals biological determinants and translational implications for ADC therapy.NPJ precision oncology · 2026Article
- Evaluating datopotamab deruxtecan (Dato-DXd) as a novel treatment option for EGFR-mutated non-small cell lung cancer.Future oncology (London, England) · 2026Review
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.Breast cancer research and treatment · 2026Review
- Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology.Pharmaceutics · 2026Review
- Datopotamab deruxtecan in solid tumors: Recent research progress and clinical applications.Frontiers in oncology · 2026Review
- Evolving treatment strategies for HER2-altered non-small-cell lung cancer: the rise of TKIs and ADCs.Frontiers in oncology · 2026Review
- Expression of antibody-drug conjugate targets in post-mortem samples of breast cancer metastases and normal tissue.Nature communications · 2025Article
- Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).RSC advances · 2025Review
- Unexpected Long-Term Survival and Downstaging in Oligometastatic Non-Small Cell Lung Cancer Treated with Multimodal Therapy.Journal of clinical medicine · 2025Article
- Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
purposeDatopotamab deruxtecan (Dato-DXd) is a humanized anti-trophoblast cell-surface antigen-2 (TROP2) IgG1 mAb linked to a potent topoisomerase I inhibitor payload (DXd). Dato-DXd has already shown antitumor activity in breast cancer; however, the determinants of response, including the importance of TROP2 expression, remain unclear. We tested the activity of Dato-DXd in a panel of breast cancer patient-derived xenografts (BCX) varying in TROP2 expression. EXPERIMENTAL
designThe antitumor activity of Dato-DXd and isotype-control-DXd (IgG-DXd) was assessed against 11 BCXs varying in TROP2 expression, 10 representing tumors postneoadjuvant chemotherapy. Pharmacodynamic effects were assessed at 24 and 72 hours. The effects of TROP2 expression on Dato-DXd activity was assessed in vitro and in vivo using viral overexpression in BCX-derived cell lines.
resultsModels differed in their sensitivity to both Dato-DXd and IgG-DXd. Dato-DXd (10 mg/kg) led to objective response in 4 (36%) models and statistically significant prolongation of event-free survival in 8 (73%) models, whereas IgG-DXd (10 mg/kg) led to response in 1 (9%) and prolonged event-free survival in 3 (27%) models. TROP2 RNA and protein were significantly higher in Dato-DXd-sensitive models. In isogenic cell lines derived from Dato-DXd-resistant BCXs, overexpression of TROP2 conferred Dato-DXd antitumor activity in vitro and in vivo. Dato-DXd increased γH2AX and phospho-KAP1 in the two Dato-DXd-sensitive BCXs but not in a Dato-DXd-resistant BCX. In Dato-DXd-sensitive models, antitumor activity was enhanced in combination with a PARP inhibitor, olaparib.
conclusionsDato-DXd is active in breast cancer models. Dato-DXd has TROP2-dependent and -independent mediators of activity; however, high TROP2 expression enhances Dato-DXd antitumor activity.
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