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

Animals Benzamides / pharmacology Breast Neoplasms / drug therapy Cell Line, Tumor Drug Resistance, Neoplasm / drug effects Female Heterografts / drug effects 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

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
31 03 2021
Historique:
received: 28 08 2020
accepted: 26 02 2021
entrez: 1 4 2021
pubmed: 2 4 2021
medline: 20 4 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-021-22303-z PMID: 33790302 PMC: PMC8012607
pubmed: 33790302
doi: 10.1038/s41467-021-22303-z
pii: 10.1038/s41467-021-22303-z
pmc: PMC8012607
doi:

Substances chimiques

Benzamides 0
Morpholines 0
Piperazines 0
Protein Kinase Inhibitors 0
Pyridines 0
Pyrimidines 0
vistusertib 0BSC3P4H5X
palbociclib G9ZF61LE7G

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1998

Subventions

Organisme : Cancer Research UK
ID : C9545/A24042
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Medical Research Council
ID : MR/M008975/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Cancer Research UK
ID : A16942
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A29580
Pays : United Kingdom

Investigateurs

H R Ali (HR)
M Al Sa'd (M)
S Alon (S)
S Aparicio (S)
G Battistoni (G)
S Balasubramanian (S)
R Becker (R)
B Bodenmiller (B)
E S Boyden (ES)
D Bressan (D)
A Bruna (A)
Marcel Burger (M)
C Caldas (C)
M Callari (M)
I G Cannell (IG)
H Casbolt (H)
N Chornay (N)
Y Cui (Y)
A Dariush (A)
K Dinh (K)
A Emenari (A)
Y Eyal-Lubling (Y)
J Fan (J)
A Fatemi (A)
E Fisher (E)
E A González-Solares (EA)
C González-Fernández (C)
D Goodwin (D)
W Greenwood (W)
F Grimaldi (F)
G J Hannon (GJ)
O Harris (O)
S Harris (S)
C Jauset (C)
J A Joyce (JA)
E D Karagiannis (ED)
T Kovačević (T)
L Kuett (L)
R Kunes (R)
Yoldaş A Küpcü (YA)
D Lai (D)
E Laks (E)
H Lee (H)
M Lee (M)
G Lerda (G)
Y Li (Y)
A McPherson (A)
N Millar (N)
C M Mulvey (CM)
F Nugent (F)
C H O'Flanagan (CH)
M Paez-Ribes (M)
I Pearsall (I)
F Qosaj (F)
A J Roth (AJ)
O M Rueda (OM)
T Ruiz (T)
K Sawicka (K)
L A Sepúlveda (LA)
S P Shah (SP)
A Shea (A)
A Sinha (A)
A Smith (A)
S Tavaré (S)
S Tietscher (S)
I Vázquez-García (I)
S L Vogl (SL)
N A Walton (NA)
A T Wassie (AT)
S S Watson (SS)
J Weselak (J)
S A Wild (SA)
E Williams (E)
J Windhager (J)
T Whitmarsh (T)
C Xia (C)
P Zheng (P)
X Zhuang (X)

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Auteurs

Dimitra Georgopoulou (D)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Maurizio Callari (M)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Oscar M Rueda (OM)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
ORCID: 0000-0003-0008-4884

Abigail Shea (A)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Alistair Martin (A)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Agnese Giovannetti (A)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
Laboratory of Clinical Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
ORCID: 0000-0001-5207-7243

Fatime Qosaj (F)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Ali Dariush (A)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
Institute of Astronomy, University of Cambridge, Cambridge, UK.

Suet-Feung Chin (SF)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-5697-1082

Larissa S Carnevalli (LS)

Bioscience, Oncology, Early Oncology R&D, AstraZeneca, Cambridge, UK.
ORCID: 0000-0001-7432-0195

Elena Provenzano (E)

Breast Cancer Programme, CRUK Cambridge Centre, Cambridge, UK.
Cambridge Breast Cancer Research Unit, NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
ORCID: 0000-0003-3345-3965

Wendy Greenwood (W)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Giulia Lerda (G)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Elham Esmaeilishirazifard (E)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
Bioscience, Oncology, Early Oncology R&D, AstraZeneca, Cambridge, UK.

Martin O'Reilly (M)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Violeta Serra (V)

Experimental Therapeutics Group, Vall d'Hebron Institut d'Oncologia, Barcelona, Spain.
ORCID: 0000-0001-6620-1065

Dario Bressan (D)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
ORCID: 0000-0003-3592-699X

Gordon B Mills (GB)

Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health & Sciences University, Portland, OR, USA.
ORCID: 0000-0002-0144-9614

H Raza Ali (HR)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-7587-0906

Sabina S Cosulich (SS)

Bioscience, Oncology, Early Oncology R&D, AstraZeneca, Cambridge, UK.

Gregory J Hannon (GJ)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Alejandra Bruna (A)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.

Carlos Caldas (C)

Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK. carlos.caldas@cruk.cam.ac.uk.
Breast Cancer Programme, CRUK Cambridge Centre, Cambridge, UK. carlos.caldas@cruk.cam.ac.uk.
Cambridge Breast Cancer Research Unit, NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. carlos.caldas@cruk.cam.ac.uk.
ORCID: 0000-0003-3547-1489

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Landscapes of cellular phenotypic diversity in...
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