Although radiotherapy is effective at curing many different types of cancer, some tumours are recognised as being resistant to radiation treatment.
The presence of genetic and epigenetic changes in tumour cells can lead to ‘intrinsic radioresistance’, whilst the presence of an abnormal tumour microenvironment such as tumour hypoxia can lead to ‘extrinsic radioresistance’
Our laboratory research has involved large-scale drug and siRNA screens to find new ways of increasing tumour radiosensitivity. Our aim is to use these findings to develop treatments that can be combined with radiotherapy to improve outcomes for cancer patients. For example, we previously identified that depletion of DNA polymerase theta (POLQ) induces tumour specific radiosensitisation. We subsequently established a collaboration with Cancer Research Technology to develop inhibitors against this target. This work has subsequently been spun-out into a new company (Artios) which has POLQ as its lead programme. We continue to work closely with Artios in the development of these compounds.
We aim to translate our laboratory findings into clinical trials and I am currently the Chief Investigator of two such studies. My clinical work has a strong focus on lung cancer as radiotherapy plays a key role in the management of this disease yet is still associated with poor outcomes.
Our trials often involve the use of functional imaging, such as perfusion CT scans and 18F-Misonidazole PET-CT scans, to detect changes in tumour blood flow and regions of tumour hypoxia, respectively. By performing these scans before and after drug treatment we can assess whether hypoxia has been reduced in the tumour, making it more likely to respond favourably to radiotherapy.