Abstract
BackgroundHead and neck squamous cell carcinoma (HNSCC) is the 5th most common cancer worldwide. Locally advanced HNSCC are treated with either radiation or chemo-radiotherapy, but still associated with high mortality rate, underscoring the need to develop novel therapies. Oncolytic viruses have been garnering increasing interest as anti-cancer agents due to their preferential killing of transformed cells. In this study, we evaluated the therapeutic potential of mutant vesicular stomatitis virus (VSVΔ51) against the human hypopharyngeal FaDu tumour model in vitro and in vivo.ResultsOur data demonstrated high toxicity of the virus against FaDu cells in vitro, which was associated with induction of apoptosis. In vivo, systemic injection of 1 × 109 pfu had minimal effect on tumour growth; however, when combined with two doses of ionizing radiation (IR; 5 Gy each) or a single injection of the vascular disrupting agent (ZD6126), the virus exhibited profound suppression of tumour growth, which translated to a prolonged survival in the treated mice. Concordantly, VSVΔ51 combined with ZD6126 led to a significant increase in viral replication in these tumours.ConclusionsOur data suggest that the combinations of VSVΔ51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the 5th most common cancer worldwide
We evaluated the efficacy of VSVΔ51 against the human FaDu hypopharyngeal squamous cell carcinoma model either as a single agent, or combined with radiation therapy (RT) or the vascular disrupting agent ZD6126
Combining VSVΔ51 with 4 Gy ionizing radiation (IR) led to a slight increase in apoptosis (26% vs. 22%)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the 5th most common cancer worldwide. Advanced HNSCC are treated with either radiation or chemo-radiotherapy, but still associated with high mortality rate, underscoring the need to develop novel therapies. Oncolytic viruses have been garnering increasing interest as anti-cancer agents due to their preferential killing of transformed cells. Advanced diseases are treated with either radiation or chemo-radiotherapy, but are still associated with >50% mortality rate [1,2], underscoring the need to develop novel therapeutic strategies. Oncolytic viruses have recently garnered increasing interest as anti-cancer agents due to their preferential killing of transformed cells (reviewed in [3,4]). Our data demonstrated enhanced efficacy of VSVΔ51 when combined with either RT or ZD6126 in vivo, thereby supporting the potential clinical utility of these combination strategies for head and neck cancer
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