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Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response.

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Georgopoulou, Dimitra 
Callari, Maurizio 
Shea, Abigail 
Martin, Alistair 


The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.



Animals, Benzamides, Breast Neoplasms, Cell Line, Tumor, Drug Resistance, Neoplasm, Female, Heterografts, Humans, MCF-7 Cells, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Morpholines, Piperazines, Protein Kinase Inhibitors, Pyridines, Pyrimidines, Treatment Outcome, Xenograft Model Antitumor Assays, Mice

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Nat Commun

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Springer Science and Business Media LLC


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European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (660060)
European Research Council (694620)
Cancer Research UK (C14303/A17197)
Royal Society (RP130039)
Cancer Research UK (C14303/A17197)
Cancer Research UK (22582)
Cancer Research UK (24042)
Cancer Research UK (C9545/A29580_do not transfer)
Royal Society (RSRP\R\200001)
Cancer Research UK (16942)
Medical Research Council (MR/M008975/1)
Cancer Research UK (25815)