Development of tumour specific radiation sensitising treatments

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Radiotherapy (RT) treatment plays a key role in the management of many solid tumours and involves the precise delivery of high energy X-rays to localised tumours. In the curative setting, treatment can be used alone, or in combination with chemotherapy or immunotherapy. Although technological improvements have enabled the ability to deliver novel, highly effective RT treatments such as stereotactic ablative body radiotherapy (SABR), there is no approach that is able to fully spare healthy tissues from receiving some radiotherapy, often leading to significant side-effects. Obtaining greater tumour control by simply increasing the delivered dose is therefore not an adequate solution. A more tractable approach is to develop treatments which selectively render tumours more sensitive to radiation without exerting an effect on normal tissues. We have previously conducted high-throughput compound and genetic screens to identify novel, clinically translatable targets. This has led to the development of several new compounds which we anticipate will cause tumour specific radiosensitisation. The aim of this project will be to undertake in depth pre-clinical testing of these compounds to assess their suitability as clinically useful treatments.