Imperial College London

ProfessorLucaMagnani

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Cancer Adaptation and Evolution
 
 
 
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Contact

 

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

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Acar:2019:10.1101/566950,
author = {Acar, A and Nichol, D and Fernandez-Mateos, J and Cresswell, GD and Barozzi, I and Hong, SP and Spiteri, I and Stubbs, M and Burke, R and Stewart, A and Vlachogiannis, G and Maley, CC and Magnani, L and Valeri, N and Banerji, U and Sottoriva, A},
doi = {10.1101/566950},
title = {Exploiting evolutionary herding to control drug resistance in cancer},
url = {http://dx.doi.org/10.1101/566950},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - <jats:title>Abstract</jats:title><jats:p>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 growth rate or increased sensitivity to another drug due to evolutionary trade-offs. This weakness can be exploited in the clinic using an approach called ‘evolutionary herding’ that aims at controlling the tumour cell population to delay or prevent resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here we present a novel approach for evolutionary herding based on a combination of single-cell barcoding, very large populations of 10<jats:sup>8</jats:sup>–10<jats:sup>9</jats:sup>cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary herding in non-small cell lung cancer, showing that herding allows shifting the clonal composition of a tumour in our favour, leading to collateral drug sensitivity and proliferative fitness costs. Through genomic analysis and single-cell sequencing, we were also able to determine the mechanisms that drive such evolved sensitivity. Our approach allows modelling evolutionary trade-offs experimentally to test patient-specific evolutionary herding strategies that can potentially be translated into the clinic to control treatment resistance.</jats:p>
AU - Acar,A
AU - Nichol,D
AU - Fernandez-Mateos,J
AU - Cresswell,GD
AU - Barozzi,I
AU - Hong,SP
AU - Spiteri,I
AU - Stubbs,M
AU - Burke,R
AU - Stewart,A
AU - Vlachogiannis,G
AU - Maley,CC
AU - Magnani,L
AU - Valeri,N
AU - Banerji,U
AU - Sottoriva,A
DO - 10.1101/566950
PY - 2019///
TI - Exploiting evolutionary herding to control drug resistance in cancer
UR - http://dx.doi.org/10.1101/566950
ER -