UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

Znati, S; Carter, R; Vasquez, M; Westhorpe, A; Shahbakhti, H; Prince, J; Vlckova, P; ... Sharma, RA; + view all (2020) Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib. Cancers , 12 (7) , Article 1878. 10.3390/cancers12071878. Green open access

[thumbnail of Loizidou_Vcancers-12-01878.pdf]
Preview
Text
Loizidou_Vcancers-12-01878.pdf - Published version

Download (8MB) | Preview

Abstract

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.

Type: Article
Title: Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/cancers12071878
Publisher version: https://doi.org/10.3390/cancers12071878
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: vandetanib; radiotherapy; 3D models; immunocompetent; syngeneic; animal model; vascular endothelial growth factor receptor-2; angiogenesis; radiosensitiser; hepatocellular carcinoma
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10106181
Downloads since deposit
11Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item