Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response.
Details
Serval ID
serval:BIB_6CE9EEBF7E86
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response.
Journal
Nature communications
Working group(s)
IMAXT Consortium
Contributor(s)
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., Zhuang X.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
31/03/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
1998
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
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.
Keywords
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, Mice, SCID, Morpholines/pharmacology, Piperazines/pharmacology, Protein Kinase Inhibitors/pharmacology, Pyridines/pharmacology, Pyrimidines/pharmacology, Treatment Outcome, Xenograft Model Antitumor Assays/methods
Pubmed
Web of science
Open Access
Yes
Create date
30/04/2021 18:16
Last modification date
12/01/2022 8:10
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