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


Authors: Georgopoulou, D.; Callari, M.; Rueda, O. M.; Shea, A.; Martin, A.; Giovannetti, A.; Qosaj, F.; Dariush, A.; Chin, S. F.; Carnevalli, L. S.; Provenzano, E.; Greenwood, W.; Lerda, G.; Esmaeilishirazifard, E.; O’Reilly, M.; Serra, V.; Bressan, D.; IMAXT Consortium; Mills, G. B.; Ali, H. R.; Cosulich, S. S.; Hannon, G. J.; Bruna, A.; Caldas, C.
Contributors: McPherson, A.; Roth, A. J.; Shah, S. P.; Vázquez-García, I.
Article Title: Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response
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. © 2021, The Author(s).
Keywords: flow cytometry; phenotype; gene; murinae; tumor; cell; drug; cancer
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-03-31
Start Page: 1998
Language: English
DOI: 10.1038/s41467-021-22303-z
PUBMED: 33790302
PROVIDER: scopus
PMCID: PMC8012607
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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  1. Sohrab Prakash Shah
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