Imperial College London
Alternate

Dr Ernesto Yagüe

Faculty of Medicine, Department of Surgery & Cancer

Non-Clinical Lecturer in Cancer Cell Biology
 
 
 
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Contact

 

+44 (0)20 7594 2802ernesto.yague Website

 
 
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Location

 

Cancer Research Centre, room 135ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kumar:2023:10.1016/j.gene.2022.146930,
author = {Kumar, U and Castellanos-Uribe, M and May, ST and Yagüe, E},
doi = {10.1016/j.gene.2022.146930},
journal = {Gene},
title = {Adaptive resistance is not responsible for long-term drug resistance in a cellular model of triple negative breast cancer},
url = {http://dx.doi.org/10.1016/j.gene.2022.146930},
volume = {850},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Resistance to cancer therapeutics represents a leading cause of mortality and is particularly important in cancers, such as triple negative breast cancer, for which no targeted therapy is available, as these are only treated with traditional chemotherapeutics. Cancer, as well as bacterial, drug resistance can be intrinsic, acquired or adaptive. Adaptive cancer drug resistance is gaining attention as a mechanism for the generation of long-term drug resistance as is the case with bacterial antibiotic resistance. We have used a cellular model of triple negative breast cancer (CAL51) and its drug resistance derivative (CALDOX) to gain insight into genome-wide expression changes associated with long-term doxorubicin (a widely used anthracycline for cancer treatment) resistance and doxorubicin-induced stress. Previous work indicates that both naïve and resistance cells have a functional p53-p21 axis controlling cell cycle at G1, although this is not a driver for drug resistance, but down-regulation of TOP2A (topoisomerase IIα). As expected, CALDOX cells have a signature characterized, in addition to down-regulation of TOP2A, by genes and pathways associated with drug resistance, metastasis and stemness. Both CAL51 and CALDOX stress signatures share 12 common genes (TRIM22, FAS, SPATA18, SULF2, CDKN1A, GDF15, MYO6, CXCL5, CROT, EPPK1, ZMAT3 and CD44), with roles in the above-mentioned pathways, indicating that these cells have similar functional responses to doxorubicin relaying on the p53 control of apoptosis. Eight genes are shared by both drug stress signatures (in CAL51 and CALDOX cells) and CALDOX resistant cells (FAS, SULF2, CDKN1A, CXCL5, CD44, SPATA18, TRIM22 and CROT), many of them targets of p53. This corroborates experimental data indicating that CALDOX cells, even in the absence of drug, have activated, at least partially, the p53-p21 axis and DNA damage response. Although this eight-gene signature might be an indicator of adaptive resistance, as thi
AU  - Kumar,U
AU  - Castellanos-Uribe,M
AU  - May,ST
AU  - Yagüe,E
DO  - 10.1016/j.gene.2022.146930
PY  - 2023///
SN  - 0378-1119
TI  - Adaptive resistance is not responsible for long-term drug resistance in a cellular model of triple negative breast cancer
T2  - Gene
UR  - http://dx.doi.org/10.1016/j.gene.2022.146930
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36195266
UR  - http://hdl.handle.net/10044/1/100198
VL  - 850
ER  -
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