1. Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response
- Author
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Sabina S Cosulich, Abigail Shea, Maurizio Callari, A. Dariush, Elena Provenzano, Martin O'Reilly, Carlos Caldas, Dimitra Georgopoulou, Agnese Giovannetti, Oscar M. Rueda, Gregory J. Hannon, Suet-Feung Chin, Giulia Lerda, Elham Esmaeilishirazifard, Alistair Martin, Violeta Serra, Fatime Qosaj, Wendy Greenwood, Dario Bressan, Larissa S. Carnevalli, Alejandra Bruna, H. Raza Ali, Gordon B. Mills, Rueda, Oscar M [0000-0003-0008-4884], Giovannetti, Agnese [0000-0001-5207-7243], Chin, Suet-Feung [0000-0001-5697-1082], Carnevalli, Larissa S [0000-0001-7432-0195], Provenzano, Elena [0000-0003-3345-3965], Serra, Violeta [0000-0001-6620-1065], Bressan, Dario [0000-0003-3592-699X], Mills, Gordon B [0000-0002-0144-9614], Ali, H Raza [0000-0001-7587-0906], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository, IMAXT Consortium, Ali, H.R., Al Sa'd, M., Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E.S., Bressan, D., Bruna, A., Burger, M., Caldas, C., Callari, M., Cannell, I.G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E.A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G.J., Harris, O., Harris, S., Jauset, C., Joyce, J.A., Karagiannis, E.D., Kovačević, T., Kuett, L., Kunes, R., Küpcü, Y.A., Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C.M., Nugent, F., O'Flanagan, C.H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A.J., Rueda, O.M., Ruiz, T., Sawicka, K., Sepúlveda, L.A., Shah, S.P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S.L., Walton, N.A., Wassie, A.T., Watson, S.S., Weselak, J., Wild, S.A., Williams, E., Windhager, J., Whitmarsh, T., Xia, C., Zheng, P., and Zhuang, X.
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0301 basic medicine ,Pyridines ,Science ,Tumour heterogeneity ,Morpholines ,Cell ,General Physics and Astronomy ,Breast Neoplasms ,Drug resistance ,Mice, SCID ,Biology ,Animals ,Benzamides/pharmacology ,Breast Neoplasms/drug therapy ,Breast Neoplasms/genetics ,Breast Neoplasms/metabolism ,Cell Line, Tumor ,Drug Resistance, Neoplasm/drug effects ,Drug Resistance, Neoplasm/genetics ,Female ,Heterografts/drug effects ,Heterografts/metabolism ,Humans ,MCF-7 Cells ,Mice, Inbred NOD ,Mice, Knockout ,Morpholines/pharmacology ,Piperazines/pharmacology ,Protein Kinase Inhibitors/pharmacology ,Pyridines/pharmacology ,Pyrimidines/pharmacology ,Treatment Outcome ,Xenograft Model Antitumor Assays/methods ,General Biochemistry, Genetics and Molecular Biology ,Article ,Piperazines ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,medicine ,Mass cytometry ,Protein Kinase Inhibitors ,Multidisciplinary ,Genetic heterogeneity ,Cancer ,General Chemistry ,medicine.disease ,Biobank ,Phenotype ,Xenograft Model Antitumor Assays ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Pyrimidines ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Benzamides ,Cancer research ,Heterografts - Abstract
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., The heterogeneity of breast cancer has a major role in drug response and resistance. In this study, the authors use patient-derived tumour xenografts as a platform for drug testing and correlation with single-cell proteomic phenotypes characterized by mass cytometry.
- Published
- 2021
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