biostudies-literatureLiu XNCI NIH HHSNIGMS NIH HHS6632-6643https://www.ebi.ac.uk/biostudies/studies/S-EPMC8120216biostudies-literatureUnknown11(13)Triple-negative breast cancer (TNBC) is one of the most aggressive and metastatic breast cancer subtypes lacking targeted therapy. Our recent work demonstrated that circulating tumor cell (CTC) clusters and polyclonal metastasis of TNBC are driven by aggregation of CD44+ cancer stem cells (CSC) and associated with an unfavorable prognosis, such as low overall survival. However, there is no existing therapeutic that can specifically block CTC or CSC cluster formation. Methods: Using patient-derived xenograft (PDX) models, we established an ex vivo tumor cell clustering assay for a pilot screening of blockade antibodies. After identifying EGFR as a target candidate, we modulated the gene expression and inhibited its kinase activity to determine its functional importaTheranosticsEGFR inhibition blocks cancer stem cell clustering and lung metastasis of triple negative breast cancer.PMC8120216P20 GM121327T32 CA009560T32 GM008061R01 CA245699Liu HKawaguchi MChang YFDashzeveg NKPatel DCristofanilli MRamos EKAdorno-Cruz VTaftaf RLiu XZhang YJia YSchuster EJEl-Shennawy LfalseEGFR inhibition blocks cancer stem cell clustering and lung metastasis of triple negative breast cancer.Triple-negative breast cancer (TNBC) is one of the most aggressive and metastatic breast cancer subtypes lacking targeted therapy. Our recent work demonstrated that circulating tumor cell (CTC) clusters and polyclonal metastasis of TNBC are driven by aggregation of CD44+ cancer stem cells (CSC) and associated with an unfavorable prognosis, such as low overall survival. However, there is no existing therapeutic that can specifically block CTC or CSC cluster formation. Methods: Using patient-derived xenograft (PDX) models, we established an ex vivo tumor cell clustering assay for a pilot screening of blockade antibodies. After identifying EGFR as a target candidate, we modulated the gene expression and inhibited its kinase activity to determine its functional importa2021-01-01T00:00:00Z20212025-04-18T17:40:00.877Z2025-04-07T05:12:00.152ZS-EPMC81202163399568110.7150/thno.57706