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Micro-pharmacokinetic models of tumour radiosensitisation by DNA-PK inhibitors

By Mrs Cho Hong

Radiotherapy plays a central role in the management of cancer.

Mrs Cho Hong, University of Auckland (Post-doctoral Fellowship)

DNA-dependent protein kinase (DNA- PK) exerts a key role in repair of radiation-induced DNA damage and acts as a resistance mechanism to radiotherapy. Therefore, targeted delivery of inhibitors of DNA-PK that can selectively sensitise tumours to radiation can potentially improve clinical outcomes. Existing DNA-PK inhibitors sensitise tumour cells to radiotherapy, but also cause normal tissue toxicity.

Research led by Associate Professor Hay in the lab has recently discovered new, potent and tumour-selective inhibitors of DNA-PK. Critical to the preclinical development of these prodrugs are predictive models of pharmacokinetics (PK) and pharmacodynamics (PD) within tumours. This project will allow Cho Hong to develop PK/PD models that accurately predict anti-tumour activity and to identify the most active prodrugs for preclinical evaluation. The tools Cho will develop in this project will aid in the discovery and development of other new drugs for cancer treatment.