DNA-damage response science in radiotherapy

We are applying our innovative 3D culture system for mouse and human primary tissues (a system known as epithelioid culture) to understand the molecular mechanisms by which normal cells and mutant cancer progenitor cells show different responses to radiotherapy treatments. We are studying the role of some mutations, such as NOTCH1 and TP53, in oral and oesophageal normal epithelia during the very early events of tumour formation.

We are also involved in the characterisation of the FLASH effect in normal and tumour tissues together with Professor Karen Kirby (Manchester) and Dr Kristoffer Petersson (Oxford). FLASH treatment is based on delivering radiotherapy at ultra-high dose-rates (typically greater than 40 Gy/s) and it appears to offer increased normal tissue sparing, in comparison to conventional dose rate radiotherapy, while still suppressing tumour growth. This work will investigate a broad range of physical (dose, dose-rate, radiation quality, and pulse structure) and hypoxic conditions which will be critical in determining the optimum parameters to realise FLASH in the clinic. Now we are analysing the differential induction of DNA double strand breaks between conventional, FLASH proton, and FLASH electron radiotherapies.

Evaluating clinically-relevant radiotherapy tumour models

This theme is focused on creating cancer models and methods that help us to robustly test new radiotherapy strategies. We are testing different ways of combining radiotherapy with chemotherapy for improved outcomes. We apply state-of-the-art imaging methods to watch tumours responding to treatment, and are also creating new computational analyses to understand how we can enhance response to radiotherapy and mitigate resistance.