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Drug sensitivity is a major determinant influencing the efficiency of cancer treatment, and its evaluation faces critical challenges due to the cancer cell heterogeneity. Herein, a droplet-driven compartmentalization array (SCell chip) is presented to uncover single-cell trastuzumab sensitivity. Leveraging the differential flow resistance principle, the chip enables the flexible generation of single droplets orderly situated at designated spots. The single droplet includes parallel hydrodynamic microtraps empowers efficient compartments for single cell capture, and culture, and employs apt-functionalized microbeads to immune-affinity capture single cell extracellular vesicles (EVs). The pairing capture of single cells and their EVs using single beads allows simultaneous identification of EVs and their original cells. The protein profiles (HER2 and CD63) and anti-cancer drug challenge revealed the cellular/EVs secretion heterogeneity at the single cell level and cell susceptibility to trastuzumab, further confirming that this chip achieves discriminating and predicting single breast cancer cells with different trastuzumab sensitivity using single cell/EVs profiling strategy. Furthermore, this analysis process retains the cell viability of measured cells to promote downstream detection integration. Overall, the SCell chip offers new avenues for single-cell analysis and exhibits great potential for cancer diagnostic and targeted treatment.
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http://dx.doi.org/10.1002/smll.202410388 | DOI Listing |
Mol Cancer Ther
September 2025
Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Trastuzumab deruxtecan (T-DXd) is a HER2-targeting antibody-drug conjugate (ADC) with efficacy across adult cancers exhibiting variable HER2 expression. Prior studies demonstrating HER2 expression in osteosarcoma (OS) motivated a clinical trial of T-DXd in pediatric and adolescent/young adults with OS but was terminated early for inactivity. We evaluated the activity of T-DXd using OS patient-derived xenograft (PDX) models and found a 22% objective response rate despite no detectable HER2 expression across PDXs tested.
View Article and Find Full Text PDFInorg Chem Front
August 2025
School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital London UK
Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples. Typically, these specimens are exposed to a panel of labelled antibodies , after sample collection. Here, we have developed a rhodium-labelled immunoconjugate of the HER2-targeted therapeutic IgG1 antibody, trastuzumab, and evaluated its biodistribution using mass cytometry techniques.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
August 2025
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine Nanjing Medical University Nanjing, China. Electronic address:
Resistance to HER2-targeted therapies presents a major challenge in the treatment of patients with HER2-positive breast cancer. N(6)-methyladenosine (m6A) modification plays a critical role in tumor progression; however, its role in mediating resistance to anti-HER2 therapy remains poorly defined. In trastuzumab-resistant HER2-positive breast cancer tissues, METTL14 expression is significantly upregulated and correlates with poor trastuzumab response.
View Article and Find Full Text PDFLab Invest
August 2025
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. Electronic address:
The recent approval of antibody drug conjugates (ADCs) targeting HER2 (like Trastuzumab Deruxtecan or T-DXd) have led to challenges for the immunohistochemical (IHC) companion diagnostic test since the test was optimized for gene amplified levels of HER2. Here we develop and validate an objective test for low level HER2 expression toward more accurate selection of patients for T-DXd. We validated the high-sensitivity HER2 assay using a mix of the requirements for an IHC assay and that of a ligand binding assay.
View Article and Find Full Text PDFZhonghua Xin Xue Guan Bing Za Zhi
August 2025
Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
To explore the application value of machine learning algorithms in constructing a predictive model for cardiovascular toxicity in breast cancer patients receiving anthracycline-based chemotherapy. This study was a retrospective cohort study. The female patients with breast cancer who received anthracyclines in the Affiliated Cancer Hospital of Xinjiang Medical University from January 2020 to December 2023 were enrolled.
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