Head and neck squamous cell carcinoma (HNSCC) is the most common cancer type in the head and neck region, accounting for the 5th most common cancer worldwide [
1]. Locally 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]). Among these, the mutant variant of vesicular stomatitis virus (VSV) has been evaluated in different tumour models, demonstrating promising results as either single agent or in combination with other treatment modalities [
5‐
7]. We had previously demonstrated the exquisite sensitivity of EBV-positive nasopharyngeal carcinoma (NPC) to a mutant VSV (VSVΔ51), which has a single amino acid deletion in the VSV M protein, rendering lethality to cancer cells, whilst sparing normal cells [
8]. Building upon this observation, herein 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. ZD6126 is a colchicine prodrug derivative that is metabolized
in vivo to yield ZD6126 phenol, which then selectively binds to the colchicine-binding site of tubulin; this disrupts the microtubule structure, largely responsible for the structure and morphology of dividing and immature vascular endothelial cells [
9]. 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.