Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

Cancers
Sami A ZnatiRicky A Sharma

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. 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. 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. In 2D and 3D studies in vitro and in a syngeneic model in vivo, the combination of vandetanib plus radiotherapy was more efficacious than ei...Continue Reading

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Citations

Dec 17, 2020·Cancers·Luigi Buonaguro
May 28, 2021·Frontiers in Oncology·Marike W van GisbergenLudwig J Dubois
Jun 25, 2021·Human & Experimental Toxicology·Y-F Gu, L-T Kong
Aug 13, 2021·Frontiers in Oncology·Mengke NiuKongming Wu
Sep 4, 2021·Clinical Oncology : a Journal of the Royal College of Radiologists·J SinghS X Pfister
Sep 6, 2021·International Journal of Radiation Oncology, Biology, Physics·Josephine GörteNils Cordes

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Methods Mentioned

BETA
Transfection
glycosylation
Fluorescence Assisted Cell Sorting

Key Resources (RRID) Mentioned

Addgene_31183

Software Mentioned

TASI OrganoSeg
Graphpad Prism
ImageJ

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