Lead supervisor: Professor Alison Curnow, Associate Professor, College of Medicine and Health
Dr Mark Wood, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
Dr Alexis Perry, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
Non-melanoma skin cancer (NMSC) is the most common type of cancer worldwide and is predominantly caused by the ubiquitous environmental carcinogen, ultraviolet radiation. Caucasian NMSC prevalence is rapidly increasing, with over 80,000 new cases reported in England in 2008. NHS skin cancer costs are predicted to approach £180M by 2020 (Vallejo-Torres et al., 2014, J. Public Health, 36;140-148). Photodynamic therapy (PDT) is a relatively new way to treat this type of cancer. A cream containing a drug is put on the skin and the cancer cells transform it into a light sensitive active compound over a period of a few hours. Shining light then kills the cancer, without damaging the surrounding healthy skin. This means that healing occurs without scarring or disfigurement (unlike standard surgical treatment). PDT is a cost-effective, nurse-led and cosmetically acceptable NMSC treatment option but ~50% of lesions are too thick to be treated effectively with one cycle of the current protocol. Optimising and improving PDT for more difficult to treat NMSC is therefore important for public health and could save considerable NHS resources.
Our previous research has indicated that one way to improve topical dermatological PDT, is to co-administer an iron chelating agent because this results in increased accumulation of the photoactive compound and thus better experimental outcomes on irradiation. The University of Exeter has also recently synthesised and patented a novel iron chelating agent (AP2-18) specifically for this purpose and this project will extend our understanding of this novel compound’s PDT enhancement potential in vitro.
Experimentation will be conducted within our laboratory facilities in the Environment and Sustainability Institute on the Penryn Campus in Cornwall. PDT will be conducted on a range of human cultured cells including both normal and neoplastic cell types such as normal human epidermal keratinocytes (NHEK; from which SCC arises), normal human fibroblasts (84BR; as controls) as well as squamous epithelial carcinoma cells (A431) and basal cell carcinoma (BCC) cells. All these cells types are available from commercial sources, negating the necessity to gain ethical approval for this investigation. Some initial preparatory work and training will also be conducted with inexpensive and easy to cultivate normal human lung fibroblasts (MRC5). Various assays to determine the cellular cytotoxicity of the new compound in comparison with existing PDT drugs will be conducted to determine the optimal treatment protocol and potential efficacy. Experimentation will also be extended as time permits to evaluate the novel compound for other non-dermatological potential PDT applications. All experimentation will be undertaken in triplicate on three separate occasions to generate robust scientific findings and appropriate blank and positive controls will employed throughout. All data will be tested for normality before conducting appropriate statistical analysis to determine any significant effects at the p < 0.05 level.
The findings of this research will make a substantial, original contribution to the current state of the art of this important and impactful research field and if successful, will help to derive improved PDT treatment outcomes for patients diagnosed with non-melanoma skin cancer.
For more information about the project and informal enquiries please contact the lead supervisor, Professor Alison Curnow ([email protected]