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Open AccessArticle

Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

1
University College London Cancer Institute, University College London, London WC1E 6BT, UK
2
Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
3
Scuola di Scienze Matematiche, Fisiche e Naturali, Università degli Studi di Firenze, 50121 Florence, Italy
4
Biocompatibles UK Ltd. (A BTG International Group Company), Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey GU15 3YH, UK
5
Division of Surgery and Interventional Science, Royal Free Campus, University College London, London NW3 2QG, UK
6
NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK
*
Authors to whom correspondence should be addressed.
Current address: National Institute for Health Research University College London Hospitals Biomedical Centre, University College London Cancer Institute, Paul O’ Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
Cancers 2020, 12(7), 1878; https://doi.org/10.3390/cancers12071878
Received: 13 May 2020 / Revised: 5 July 2020 / Accepted: 8 July 2020 / Published: 13 July 2020
(This article belongs to the Special Issue Human Hepatocellular Carcinoma (HCC))
Hepatocellular Carcinoma (HCC) is increasing in incidence worldwide and requires new approaches to therapy. The combination of anti-angiogenic drug therapy and radiotherapy is one promising new approach. The anti-angiogenic drug vandetanib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and RET proto-oncogene with radio-enhancement potential. To explore the benefit of combined vandetanib and radiotherapy treatment for HCC, we studied outcomes following combined treatment in pre-clinical models. Methods: Vandetanib and radiation treatment were combined in HCC cell lines grown in vitro and in vivo. In addition to 2D migration and clonogenic assays, the combination was studied in 3D spheroids and a syngeneic mouse model of HCC. Results: Vandetanib IC 50 s were measured in 20 cell lines and the drug was found to significantly enhance radiation cell kill and to inhibit both cell migration and invasion in vitro. In vivo, combination therapy significantly reduced cancer growth and improved overall survival, an effect that persisted for the duration of vandetanib treatment. Conclusion: In 2D and 3D studies in vitro and in a syngeneic model in vivo, the combination of vandetanib plus radiotherapy was more efficacious than either treatment alone. This new combination therapy for HCC merits evaluation in clinical trials. View Full-Text
Keywords: vandetanib; radiotherapy; 3D models; immunocompetent; syngeneic; animal model; vascular endothelial growth factor receptor-2; angiogenesis; radiosensitiser; hepatocellular carcinoma vandetanib; radiotherapy; 3D models; immunocompetent; syngeneic; animal model; vascular endothelial growth factor receptor-2; angiogenesis; radiosensitiser; hepatocellular carcinoma
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MDPI and ACS Style

Znati, S.; Carter, R.; Vasquez, M.; Westhorpe, A.; Shahbakhti, H.; Prince, J.; Vlckova, P.; De Vellis, C.; Bascal, Z.; Loizidou, M.; Sharma, R.A. Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib. Cancers 2020, 12, 1878. https://doi.org/10.3390/cancers12071878

AMA Style

Znati S, Carter R, Vasquez M, Westhorpe A, Shahbakhti H, Prince J, Vlckova P, De Vellis C, Bascal Z, Loizidou M, Sharma RA. Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib. Cancers. 2020; 12(7):1878. https://doi.org/10.3390/cancers12071878

Chicago/Turabian Style

Znati, Sami; Carter, Rebecca; Vasquez, Marcos; Westhorpe, Adam; Shahbakhti, Hassan; Prince, Jessica; Vlckova, Petra; De Vellis, Chiara; Bascal, Zainab; Loizidou, Marilena; Sharma, Ricky A. 2020. "Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib" Cancers 12, no. 7: 1878. https://doi.org/10.3390/cancers12071878

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