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Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib
Sami Znati1, Rebecca Carter1, Marcos Vasquez1
1University College London Cancer Institute, University College London, London WC1E 6BT, UK.
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.
Insights
Combining vandetanib, an anti-angiogenic drug, with radiotherapy shows promise for treating hepatocellular carcinoma (HCC). This combination therapy significantly reduced tumor growth and improved survival in preclinical models, warranting clinical trials.
Area of Science:
- Hepatocellular Carcinoma (HCC) research
- Cancer therapy development
- Radiotherapy and anti-angiogenic drug combinations
Background:
- Hepatocellular Carcinoma (HCC) incidence is rising globally, necessitating novel therapeutic strategies.
- Anti-angiogenic drug therapy combined with radiotherapy presents a promising avenue for HCC treatment.
- Vandetanib, a tyrosine kinase inhibitor, targets VEGFR-2 and RET, showing potential for radio-enhancement.
Purpose of the Study:
- To investigate the efficacy of combining vandetanib with radiotherapy for Hepatocellular Carcinoma (HCC).
- To evaluate the therapeutic benefits of this combination in preclinical HCC models.
Main Methods:
- Combination therapy with vandetanib and radiation was assessed in vitro (2D/3D cell cultures) and in vivo (syngeneic mouse model of HCC).
- Assays included 2D migration, clonogenic assays, and 3D spheroid studies.
- In vivo studies utilized a syngeneic mouse model to evaluate tumor growth and survival.
Main Results:
- Vandetanib significantly enhanced radiation-induced cancer cell death and inhibited cell migration and invasion in vitro.
- Combination therapy demonstrated a significant reduction in tumor growth in vivo.
- Improved overall survival was observed in the preclinical model, persisting during vandetanib treatment.
Conclusions:
- The combination of vandetanib and radiotherapy proved more effective than either monotherapy in both in vitro and in vivo HCC models.
- This novel combination therapy for HCC warrants further investigation in clinical trials.
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