Imperial College London
Alternate

ProfessorLakiBuluwela

Faculty of Medicine, Department of Surgery & Cancer

Professor of Cancer Medicine
 
 
 
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Contact

 

+44 (0)20 7594 2812l.buluwela

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

133ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mayayo-Peralta:2021:10.3390/cancers13246314,
author = {Mayayo-Peralta, I and Faggion, B and Hoekman, L and Morris, B and Lieftink, C and Goldsbrough, I and Buluwela, L and Siefert, JC and Post, H and Altelaar, M and Beijersbergen, R and Ali, S and Zwart, W and Prekovic, S},
doi = {10.3390/cancers13246314},
journal = {Cancers},
title = {Ribociclib induces broad chemotherapy resistance and EGFR dependency in ESR1 wildtype and mutant breast cancer},
url = {http://dx.doi.org/10.3390/cancers13246314},
volume = {13},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - While endocrine therapy is highly effective for the treatment of oestrogen receptor-α (ERα)-positive breast cancer, a significant number of patients will eventually experience disease progression and develop treatment-resistant, metastatic cancer. The majority of resistant tumours remain dependent on ERα-action, with activating ESR1 gene mutations occurring in 15–40% of advanced cancers. Therefore, there is an urgent need to discover novel effective therapies that can eradicate cancer cells with aberrant ERα and to understand the cellular response underlying their action. Here, we evaluate the response of MCF7-derived, CRISPR-Cas9-generated cell lines expressing mutant ERα (Y537S) to a large number of drugs. We report sensitivity to numerous clinically approved inhibitors, including CDK4/6 inhibitor ribociclib, which is a standard-of-care therapy in the treatment of metastatic ERα-positive breast cancer and currently under evaluation in the neoadjuvant setting. Ribociclib treatment induces senescence in both wildtype and mutant ERα breast cancer models and leads to a broad-range drug tolerance. Strikingly, viability of cells undergoing ribociclib-induced cellular senescence is maintained via engagement of EGFR signalling, which may be therapeutically exploited in both wildtype and mutant ERα-positive breast cancer. Our study highlights a wide-spread reduction in sensitivity to anti-cancer drugs accompanied with an acquired vulnerability to EGFR inhibitors following CDK4/6 inhibitor treatment
AU  - Mayayo-Peralta,I
AU  - Faggion,B
AU  - Hoekman,L
AU  - Morris,B
AU  - Lieftink,C
AU  - Goldsbrough,I
AU  - Buluwela,L
AU  - Siefert,JC
AU  - Post,H
AU  - Altelaar,M
AU  - Beijersbergen,R
AU  - Ali,S
AU  - Zwart,W
AU  - Prekovic,S
DO  - 10.3390/cancers13246314
PY  - 2021///
SN  - 2072-6694
TI  - Ribociclib induces broad chemotherapy resistance and EGFR dependency in ESR1 wildtype and mutant breast cancer
T2  - Cancers
UR  - http://dx.doi.org/10.3390/cancers13246314
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000736179500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.mdpi.com/2072-6694/13/24/6314
UR  - http://hdl.handle.net/10044/1/96068
VL  - 13
ER  -
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