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Biomarker-guided drug targeting of the tumour microenvironment in radiotherapy

65 months
Approved budget:
Emeritus Professor William Wilson
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
The inefficient blood supply within tumours gives rise to severe hypoxia and extracellular acidity. This abnormal micro-environment drives growth and spread of tumours, and their resistance to chemotherapy and radiotherapy. Our primary objective is to develop new prodrugs that selectively target anticancer drugs (cytotoxins, DNA repair inhibitors) to these refractory cells. The Programme focuses on head and neck squamous cell cancer (HNSCC), the 6th most common human malignancy and the tumour type with the most compelling evidence that hypoxia limits standard-of-care chemoradiotherapy. We will develop three chemical classes of prodrugs using preclinical models of HNSCC, including 3D cell cultures and tumour xenografts derived from individual cancer patients. A central aspect of the Programme is co-development of predictive biomarkers using genomic and proteomic tools to identify patients who will benefit from these prodrugs. Our longer-term objective is to support first-in-human clinical trials in New Zealand in HNSCC and other cancer indications.