Imperial College London
Alternate

ProfessorCharlesCoombes

Faculty of Medicine, Department of Surgery & Cancer

Emeritus Professor of Medical Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2135c.coombes

 
 
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Assistant

 

Mrs Suzy Ford +44 (0)20 7594 2135

 
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Location

 

145ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hong:2019:10.1038/s41467-019-11721-9,
author = {Hong, SP and Lombardo, Y and Chan, TE and Corleone, G and Rotmensz, N and Magnani, L and Bravaccini, S and Rocca, A and Pruneri, G and McEwen, KR and Coombes, RC and Barozzi, I},
doi = {10.1038/s41467-019-11721-9},
journal = {Nature Communications},
title = {Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy},
url = {http://dx.doi.org/10.1038/s41467-019-11721-9},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare sub population of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. We find evidence for sub-clonal expression of a PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers.
AU  - Hong,SP
AU  - Lombardo,Y
AU  - Chan,TE
AU  - Corleone,G
AU  - Rotmensz,N
AU  - Magnani,L
AU  - Bravaccini,S
AU  - Rocca,A
AU  - Pruneri,G
AU  - McEwen,KR
AU  - Coombes,RC
AU  - Barozzi,I
DO  - 10.1038/s41467-019-11721-9
PY  - 2019///
SN  - 2041-1723
TI  - Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-019-11721-9
UR  - http://hdl.handle.net/10044/1/72549
VL  - 10
ER  -
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