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

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-22303-z

2041-1723

Dimitra Georgopoulou, Maurizio Callari, Oscar M. Rueda, Abigail Shea, Alistair Martin, Agnese Giovannetti, Fatime Qosaj, A. Dariush, Suet‐Feung Chin, Larissa S. Carnevalli, Elena Provenzano, Wendy Greenwood, Giulia Lerda, Elham Esmaeilishirazifard, Martin O’Reilly, Violeta Serra, Dario Bressan, H. Raza Ali, M. Al Sa’d, Shahar Alon, Samuel Aparício, Giorgia Battistoni, Shankar Balasubramanian, Robert O. Becker, Bernd Bodenmiller, E. S. Boyden, Dario Bressan, Alejandra Bruna, Marcel Burger, Carlos Caldas, Maurizio Callari, Ian G. Cannell, Helen Casbolt, N. Chornay, Yi Cui, A. Dariush, K. Dinh, A. Emenari, Y. Eyal-Lubling, Jean Fan, Ali Fatemi, Edward A. Fisher, E. A. González-Solares, C. Gónzalez-Fernández, Douglas C. Goodwin, Wendy Greenwood, Francesco Grimaldi, Gregory J. Hannon, Owen Harris, Shelley Harris, Cristina Jauset, Johanna A. Joyce, Emmanouil D. Karagiannis, Tatjana Kovačević, Laura Kuett, Russell Kunes, Yoldaş A. Küpcü, Daniel Lai, Emma Laks, Hsuan Lee, M. Lee, Giulia Lerda, Y. Li, Andrew McPherson, Neal L. Millar, Claire M. Mulvey, Fiona Nugent, Ciara H. O’Flanagan, Marta Pàez‐Ribes, I. Pearsall, Fatime Qosaj, Andrew Roth, Oscar M. Rueda, Tamara Ruiz, Kirsty Sawicka, Leonardo A. Sepúlveda, Sohrab P. Shah, Abigail Shea, Anubhav Sinha, Adrian L. Smith, S. Tavaré, Sandra Tietscher, Ignacio Vázquez-Garćıa, Siegfried Vogl, N. A. Walton, Asmamaw T. Wassie, Spencer S. Watson, Joanna Weselak, Sonja Wild, Elena Williams, Jonas Windhager, Tristan Whitmarsh, C. Xia, Ping Zheng, Xiaowei Zhuang, Gordon B. Mills, H. Raza Ali, Sabina S. Cosulich, Gregory J. Hannon, Alejandra Bruna, Carlos Caldas,

Breast Cancer Treatment Studies

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.