Imperial College London
Alternate

ProfessorEricAboagye

Faculty of Medicine, Department of Surgery & Cancer

Professor
 
 
 
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Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

GN1Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Evans:2022:10.1016/j.ejca.2022.09.009,
author = {Evans, JS and Beaumont, J and Braga, M and Masrour, N and Mauri, F and Beckley, A and Butt, S and Karali, CS and Cawthorne, C and Archibald, S and Aboagye, EO and Sharma, R},
doi = {10.1016/j.ejca.2022.09.009},
journal = {European Journal of Cancer},
pages = {110--120},
title = {Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy},
url = {http://dx.doi.org/10.1016/j.ejca.2022.09.009},
volume = {176},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundSomatostatin receptor-2 (SSTR2) is expressed on cell surface of neuroendocrine neoplasias; its presence is exploited for the delivery of peptide receptor radionuclide therapy (PRRT). Patients with no or low expression of SSTR2 are not candidates for PRRT. SSTR2 promotor undergoes epigenetic modification, known to regulate gene expression. We investigated whether the demethylation agent, guadecitabine, could enhance the expression of SSTR2 in NET models, using radioligand uptake/PET imaging as a biomarker of epigenetic modification.MethodsThe effects of guadecitabine on the transcriptional, translational, and functional regulation of SSTR2 both in vitro and in vivo using low (QGP-1) and high (BON-1) methylated neuroendocrine neoplasia models was characterised. Promotor region methylation profiling of clinical samples (n = 61) was undertaken. Safety of combination guadecitabine and PRRT was assessed in vivo.ResultsPyrosequencing of cell lines illustrated differential methylation indices – BON: 1 94%, QGP: 1 21%. Following guadecitabine treatment, a dose-dependent increase in SSTR2 in BON-1 at a transcriptional, translational, and functional levels using the SSTR2-directed radioligand, 18F-FET-βAG-TOCA ([18F]-FETO) (150% increase [18F]-FETO uptake, p < 0.05) was observed. In vivo, guadecitabine treatment resulted in a 70% increase in [18F]-FETO uptake in BON-1 tumour models compared models with low baseline percentage methylation (p < 0.05). No additive toxicity was observed with the combination treatment of PRRT and guadecitabine in vivo. Methylation index in clinical samples was 10.5% compared to 5.2% in controls (p = 0.03) and correlated with SSTR2 expression (Wilcoxon rank sign −3.75,p < 0.01).ConclusionGuadecitabine increases SSTR2 expression both in vitro and in vivo. The combination of demethylation agents with PRRT warrants further investigation.
AU  - Evans,JS
AU  - Beaumont,J
AU  - Braga,M
AU  - Masrour,N
AU  - Mauri,F
AU  - Beckley,A
AU  - Butt,S
AU  - Karali,CS
AU  - Cawthorne,C
AU  - Archibald,S
AU  - Aboagye,EO
AU  - Sharma,R
DO  - 10.1016/j.ejca.2022.09.009
EP  - 120
PY  - 2022///
SN  - 0959-8049
SP  - 110
TI  - Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy
T2  - European Journal of Cancer
UR  - http://dx.doi.org/10.1016/j.ejca.2022.09.009
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000892112500011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.sciencedirect.com/science/article/pii/S0959804922007444?via%3Dihub
UR  - http://hdl.handle.net/10044/1/101551
VL  - 176
ER  -
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