Prostate Cancer

Investigating different pathways that contribute to prostate cancer development, with the aim of improving the diagnosis, prognosis and potential therapeutic intervention of this disease. The primarily focus is on the genetics of prostate cancer biology and the contribution of different genes to the disease with a particular interest in the key role of microRNAs, small, non-coding RNA molecules that regulate gene expression. The abnormal activity of various microRNAs has been reported in different cancers, including prostate cancer, but much remains unknown about how they drive cancer progression. Therefore, the functionality of several microRNAs are being studied to understand how they link to cancer-related mechanisms such as epithelial-to-mesenchymal transition (EMT), tumour hypoxia and drug resistance. This research includes a combination of in vitro, in vivo and in silico methodologies to generate robust experimental evidence that allows evaluation of the potential of selected microRNAs as potential diagnostic and prognostic biomarkers for prostate cancer. Since microRNAs also play a role in development of many disorders, their role in other diseases, including glaucoma and cardiovascular disease, is also under investigation. Work in this area includes collaboration with a wide network of colleagues in academia, industry and clinical institutions.

We are interested in exploring how hypoxia-related mechanisms of prostate cancer progression may explain why androgen deprivation therapy in patients often fails within 2 years. We are currently investigating how combining novel drugs with existing therapies can improve tumour growth control, and prevent subsequent relapse, by impacting upon molecular pathways in the tumour cells. In particular, we are interested in targeting cancer stem cells, which are likely to contribute to malignant progression, by using hypoxia-activated prodrugs (HAPs) and AKT inhibitors. This work involves a number of in vitro and in vivo approaches, including a reliable xenograft mouse model of tumour hypoxia, which allows us to monitor longitudinal genetic and physiological changes during treatment.

This research is supported by funding from Department for Employment & Learning and Prostate Cancer UK. Our team members collaborate externally with a number of colleagues in academia and industry, including collaborators in Almac Drug Discovery and Oncotherics Ltd.