Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response.
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Date
2021-03-31ICR Author
Author
Georgopoulou, D
Callari, M
Rueda, OM
Shea, A
Martin, A
Giovannetti, A
Qosaj, F
Dariush, A
Chin, S-F
Carnevalli, LS
Provenzano, E
Greenwood, W
Lerda, G
Esmaeilishirazifard, E
O'Reilly, M
Serra, V
Bressan, D
IMAXT Consortium,
Mills, GB
Ali, HR
Cosulich, SS
Hannon, GJ
Bruna, A
Caldas, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
IMAXT Consortium
Cell Line, Tumor
Animals
Mice, Inbred NOD
Mice, Knockout
Humans
Mice, SCID
Breast Neoplasms
Benzamides
Morpholines
Piperazines
Pyridines
Pyrimidines
Protein Kinase Inhibitors
Treatment Outcome
Xenograft Model Antitumor Assays
Drug Resistance, Neoplasm
Female
MCF-7 Cells
Heterografts
Research team
Preclinical Modelling of Paediatric Cancer Evolution
Preclinical Modelling of Paediatric Cancer Evolution
Language
eng
Date accepted
2021-02-26
License start date
2021-03-31
Citation
Nature communications, 2021, 12 (1), pp. 1998 - ?
Publisher
NATURE PORTFOLIO