Developing novel therapeutic strategies to improve radiotherapy
Primary Supervisor: Associate Professor Geoff Higgins
Second Supervisor: Dr Gonzalo Rodriguez Berriguete
Project Overview
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. Our group have previously conducted high-throughput compound and genetic screens to identify novel, clinically translatable targets and compounds to specifically render tumours more sensitive to radiation. This project aims to characterise these potential therapeutic targets and develop novel therapeutic approaches against these targets. Our ultimate goal is to translate our laboratory findings into clinical trials.
Training Opportunities
The DPhil candidate will receive training on a broad variety of techniques, including high-throughput screening methods, gene editing and silencing techniques, cell death assays, assessment of DNA damage repair, cell cycle assays, and in vivo models of cancer, amongst others. The student will also have the opportunity to present their research in lab meetings, seminars and international conferences, attend different courses, and collaborate with our academic and industrial partners.
Relevant Publications
Rodriguez-Berriguete, G., Ranzani, M., Prevo, R., Puliyadi, R., Machado, N., Bolland, H.R., Millar, V., Ebner, D., Boursier, M., Cerutti, A. and Cicconi, A., 2023. Small-molecule Polθ inhibitors provide safe and effective tumor radiosensitization in preclinical models. Clinical Cancer Research, 29(8), pp.1631-1642.
Skwarski, M., McGowan, D.R., Belcher, E., Di Chiara, F., Stavroulias, D., McCole, M., Derham, J.L., Chu, K.Y., Teoh, E., Chauhan, J. and O’Reilly, D., 2021. Mitochondrial inhibitor atovaquone increases tumor oxygenation and inhibits hypoxic gene expression in patients with non–small cell lung cancer. Clinical Cancer Research, 27(9), pp.2459-2469.
Ashton, T.M., Fokas, E., Kunz-Schughart, L.A., Folkes, L.K., Anbalagan, S., Huether, M., Kelly, C.J., Pirovano, G., Buffa, F.M., Hammond, E.M. and Stratford, M., 2016. The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia. Nature communications, 7(1), p.12308.