Imperial College London
Alternate

ProfessorLucaMagnani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Principal Research Fellow
 
 
 
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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{Magnani:2022:rs.3.rs-1435182/v1,
author = {Magnani, L},
doi = {rs.3.rs-1435182/v1},
title = {Long-term multi-modal recording reveals unpredictable nongenetic adaptation routes in dormant breast cancer cells.},
url = {http://dx.doi.org/10.21203/rs.3.rs-1435182/v1},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title>        <jats:p>Patients diagnosed with hormone dependent breast cancer (HDBC) receive five or more years of adjuvant endocrine therapies (ET). Adjuvant treatment delays relapse1,2 by targeting hidden micro-metastatic deposits, yet up to 50% of treated patients experience recurrent disease, often many years after surgery1. The mechanisms driving these subtype-specific clinical dynamics are largely unknown but likely involve dormancy2. We developed two approaches to study the long-term fate of dormant cells in unprecedented details. Firstly, we took advantage of a rare cohort of patients treated upfront with first line ETs until progression to dissect the contribution of genomic events to tumour awakening. Next, we developed a first of its kind in vitro evolutionary study to systematically record adaptive strategies of individual clonal lineages in parallel unperturbed systems during a period of several months. Collectively our data suggest that ETs induce an inherently unstable persister dormant state in a stochastically selected fraction of lineages. Over time, single cells spontaneously escape dormancy and divergently adapt via heritable transcriptional reprogramming, often developing distinct collateral resistance. Overall, this study uncovers previously unsuspected roles for non-genetic plasticity during dormancy with profound clinical implications for breast cancer.</jats:p>
AU  - Magnani,L
DO  - rs.3.rs-1435182/v1
PY  - 2022///
TI  - Long-term multi-modal recording reveals unpredictable nongenetic adaptation routes in dormant breast cancer cells.
UR  - http://dx.doi.org/10.21203/rs.3.rs-1435182/v1
ER  -
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