Imperial College London

ProfessorLucaMagnani

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Cancer Adaptation and Evolution
 
 
 
//

Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
//

Location

 

137ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Acar:2020:10.1038/s41467-020-15596-z,
author = {Acar, A and Nichol, D and Fernandez-Mateos, J and Cresswell, GD and Barozzi, I and Hong, SP and Trahearn, N and Spiteri, I and Stubbs, M and Burke, R and Stewart, A and Caravagna, G and Werner, B and Vlachogiannis, G and Maley, CC and Magnani, L and Valeri, N and Banerji, U and Sottoriva, A},
doi = {10.1038/s41467-020-15596-z},
journal = {Nature Communications},
pages = {1--14},
title = {Exploiting evolutionary steering to induce collateral drug sensitivity in cancer},
url = {http://dx.doi.org/10.1038/s41467-020-15596-z},
volume = {11},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using ‘evolutionary steering’ to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108–109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance.
AU - Acar,A
AU - Nichol,D
AU - Fernandez-Mateos,J
AU - Cresswell,GD
AU - Barozzi,I
AU - Hong,SP
AU - Trahearn,N
AU - Spiteri,I
AU - Stubbs,M
AU - Burke,R
AU - Stewart,A
AU - Caravagna,G
AU - Werner,B
AU - Vlachogiannis,G
AU - Maley,CC
AU - Magnani,L
AU - Valeri,N
AU - Banerji,U
AU - Sottoriva,A
DO - 10.1038/s41467-020-15596-z
EP - 14
PY - 2020///
SN - 2041-1723
SP - 1
TI - Exploiting evolutionary steering to induce collateral drug sensitivity in cancer
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-020-15596-z
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000529513400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.nature.com/articles/s41467-020-15596-z
UR - http://hdl.handle.net/10044/1/81290
VL - 11
ER -