Contribution of autophagy to the maintenance, invasion and metastasis of melanoma stem-like sub populations.

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Mice are often used as a tool to investigate cancer, including malignant melanoma, the most deadly form of skin cancer, and the the 5th most common cancer in the UK, resulting in more than 2000 deaths annually. Although melanoma localised to the skin can be cured by surgical excision, when the tumour spreads to other parts of the body (metastasis) it is incurable, emphasising the acute need for better ways to identify and treat potentially aggressive tumours. While the use of animals in research is vital to improve our understanding of cancer biology, and to the development of new drugs to treat cancer, researchers nevertheless aim to minimise the use of animals in cancer research and wherever possible develop alternative ways through which to generate meaningful results. The principal goal of the current research proposal is therefore to develop models that replace the use of mice for the investigation of melanoma, specifically, by creating a 3D human skin equivalent model, that recreates the precise environmental conditions of the skin, to model the early stages of melanoma development and progression, as well as a zebrafish model that mimics metastasis of melanoma in the human body during later disease stages. When fully developed, these models will be used to answer important biological questions and generate crucially required novel treatment strategies for melanoma. Preliminary research has identified a particular subpopulation of tumour cells (melanoma stem-like cells) that are able to self-renew and drive tumour progression. Understanding how specific cell survival mechanisms (autophagy) contribute to the growth of these subpopulations, will enable the development of novel therapeutic strategies with improved clinical outcome.