Dr Gabrielle Grundy PhD

Head and neck cancers (HNC) predominantly affect the skin and lining of the mouth, nose and throat; and in the North West region the incidence of HNC is three times the national average. The location of tumours makes surgery and/or radiotherapy treatments difficult with sensitive organs in proximity and can severely impact quality of life. Compounded with the fact that the tumours are appreciably resistant to radiotherapy, prognosis can be poor and there is a clear need to improve the effectiveness of treatment and outcome. Overcoming radioresistance would be a major advancement so that radiotherapy doses, and thus common side-effects, could be reduced.

The objective of my research is to discover the underlying mechanisms of radioresistance in HNC cells. There is some evidence that addition of a chemotherapy drug (olaparib) can radiosensitize cultured HNC cells and improve the degree of cell death. This drug is an inhibitor that targets a family of 17 (PARP) enzymes that can modify other cellular proteins. Therefore the aim is to identify which specific PARP enzyme olaparib targets which is crucial for radiosensitizing HNC cells, but also to test other PARP inhibitors (currently in clinical trials) that have different effects on PARP family members. My interest also lies with the function of PARP enzymes other than PARP1 following DNA damage and in cancer biology.