Lay summary
The presence of low-oxygen zones (hypoxia) is a hallmark of many tumours, which confers negative prognosis and poor treatment outcomes after surgery, chemotherapy, and radiotherapy. One way to overcome this therapeutic challenge is via hypoxia-activated prodrugs (HAPs). We have developed a novel clinical candidate HAP called S-benomycin, which is highly active in many preclinical models of cancer, including of head and neck squamous cell carcinoma (HNSCC). To prepare S-benomycin for clinical trials, we will achieve three aims: an inter-species comparison of drug metabolism to inform future drug safety studies; a survey of anti-tumour efficacy across a broad panel of HNSCC models; and development of a new imaging modality, oxygen-enhanced magnetic resonance imaging (OE-MRI), as a companion diagnostic. We aim to use these data to take S-benomycin into clinical trials in New Zealand in order to improve treatment outcomes in HNSCC patients.