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

Dimitra Georgopoulou, Maurizio Callari, Oscar M. Rueda, Abigail Shea, Alistair Martin, Agnese Giovannetti, Fatime Qosaj, Ali Dariush, Suet-Feung Chin, Larissa S. Carnevalli, Elena Provenzano, Wendy Greenwood, Giulia Lerda, Elham Esmaeilishirazifard, Martin O’Reilly, Violeta Serra, Dario Bressan, Gordon B. Mills, H. Raza Ali, Sabina S. Cosulich, Gregory J. Hannon, Alejandra Bruna and Carlos Caldas ()
Additional contact information
Dimitra Georgopoulou: University of Cambridge
Maurizio Callari: University of Cambridge
Oscar M. Rueda: University of Cambridge
Abigail Shea: University of Cambridge
Alistair Martin: University of Cambridge
Agnese Giovannetti: University of Cambridge
Fatime Qosaj: University of Cambridge
Ali Dariush: University of Cambridge
Suet-Feung Chin: University of Cambridge
Larissa S. Carnevalli: Bioscience, Oncology, Early Oncology R&D, AstraZeneca
Elena Provenzano: Breast Cancer Programme, CRUK Cambridge Centre
Wendy Greenwood: University of Cambridge
Giulia Lerda: University of Cambridge
Elham Esmaeilishirazifard: University of Cambridge
Martin O’Reilly: University of Cambridge
Violeta Serra: Experimental Therapeutics Group, Vall d’Hebron Institut d’Oncologia
Dario Bressan: University of Cambridge
Gordon B. Mills: Oregon Health & Sciences University
H. Raza Ali: University of Cambridge
Sabina S. Cosulich: Bioscience, Oncology, Early Oncology R&D, AstraZeneca
Gregory J. Hannon: University of Cambridge
Alejandra Bruna: University of Cambridge
Carlos Caldas: University of Cambridge

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22303-z

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DOI: 10.1038/s41467-021-22303-z

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