Grant: Operating Grant

As cancers grow they often outstrip their blood supply which leads to hypoxic regions in tumours, where cells exist at low oxygen tension. Low oxygen status within tumours has long been known to have a profound effect on tumour aggressiveness and radiation treatment response. Cells at low oxygen concentration (hypoxic cells) are 2-3 times more resistant to radiation than cells at normal physiological oxygen levels. Anti-diabetic drugs such as metformin, which are known to reduce the consumption oxygen at the cellular level, have very recently been found to improve cancer survival rates. In this study we will investigate the link between metformin and related agents and tumour oxygenation. Our specific hypothesis being that inhibitors of oxygen consumption can be employed to induce a return to normal oxygenation of the tumour and hence increase radiation response. The primary goal will be to develop a drug treatment strategy that could be translated to the clinical radiotherapy where the tumours of patients undergoing radiotherapy would be re-oxygenated just prior to treatment in order to render them maximally responsive to treatment. About half of all patients treated for cancer receive radiation therapy and approximately half of those are cured. Temporally increasing tumour cell oxygenation could significantly increase tumour radiosensitivity which would translate into increased cure rates.