Imperial College London
Alternate

DR JAMES A HARKER

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Respiratory Science
 
 
 
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Contact

 

+44 (0)20 7594 3171j.harker

 
 
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Location

 

360Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Beloueche-Babari:2020:10.1038/s41416-019-0717-x,
author = {Beloueche-Babari, M and Casals, Galobart T and Delgado-Goni, T and Wantuch, S and Parkes, HG and Tandy, D and Harker, JA and Leach, MO},
doi = {10.1038/s41416-019-0717-x},
journal = {British Journal of Cancer},
pages = {895--903},
title = {Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration},
url = {http://dx.doi.org/10.1038/s41416-019-0717-x},
volume = {122},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundMonocarboxylate transporter 1 (MCT1) is a regulator of cell metabolism and a therapeutic target for cancer treatment. Understanding the changes in tumour function accompanying MCT1 inhibition will better characterise the anti-tumour effects of MCT1 inhibitors, potentially enabling the identification of pharmacodynamic biomarkers for the clinical development of these agents.MethodsWe assessed the impact of the MCT1 inhibitor AZD3965 on tumour metabolism and immune cell infiltration as key determinants of tumour biological function in the MCT1-dependent Raji B cell lymphoma model.ResultsTreatment of Raji xenograft-bearing severe combined immunodeficiency mice with AZD3965 led to inhibition of tumour growth paralleled with a decrease in tumour choline, as detected by non-invasive in vivo proton nuclear magnetic resonance spectroscopy. This effect was attributed to inhibition of phosphocholine de novo synthesis following decreased choline kinase α protein and messenger RNA expression that correlated with the AZD3965-induced build-up in intracellular lactate. These changes were concomitant with increased tumour immune cell infiltration involving dendritic and natural killer cells.ConclusionsOur data provide new insights into the metabolic and cellular changes that occur in the tumour microenvironment following MCT1 blockade, which may contribute to the anti-tumour activity of AZD3965 and could have potential as pharmacodynamic biomarkers of MCT1 inhibition.
AU  - Beloueche-Babari,M
AU  - Casals,Galobart T
AU  - Delgado-Goni,T
AU  - Wantuch,S
AU  - Parkes,HG
AU  - Tandy,D
AU  - Harker,JA
AU  - Leach,MO
DO  - 10.1038/s41416-019-0717-x
EP  - 903
PY  - 2020///
SN  - 0007-0920
SP  - 895
TI  - Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration
T2  - British Journal of Cancer
UR  - http://dx.doi.org/10.1038/s41416-019-0717-x
UR  - http://nature.com/articles/s41416-019-0717-x
UR  - http://hdl.handle.net/10044/1/76107
VL  - 122
ER  -
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