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Identifying genetic changes when mouth cancer begins to aid early diagnosis

Dr Guy Lyons is aiming to identify genetic changes when lip and mouth cancer first begins to try and aid early diagnosis, when treatment has a higher chance of success.

Worldwide, more than 300,000 new cases of lip and mouth cancer were estimated to have been diagnosed in 2012. Sadly almost half the people with lip and mouth cancer die from their disease.

To ensure more people survive, it is important it is detected and diagnosed early. Dr Guy Lyons explains “My project will develop methods for identifying areas of the mouth that are going to give rise to cancers before they actually do so. It uses a novel experimental model called a confetti mouse where different genes are labelled with an array of colours. This enables continuous observation of oral tissue in mice as they develop cancer and their tongues take on a multi-coloured confetti-like appearance. We will analyse their growth patterns and genes to find markers for the regions of the mouth that later become cancerous. This work couldn’t be done in any way other than studying how oral cancer actually begins in mice.

We hope that by applying such markers in patients, pre-cancerous tissue can be treated before it becomes cancerous and therefore help with cancer prevention. Our “dream” for the future is that the results from this project will enable the development of a simple paste or mouthwash that can be used routinely to screen for areas of the mouth and throat that are at risk of becoming cancer.

The outcome of this project will also enable us to undertake future investigations into the processes of how normal cells become malignant from an evolutionary perspective. Just as species of organisms evolve by acquiring mutations in their genes and undergoing natural selection, so the cells of developing tumours acquire mutations and are selected for their ability to out-compete the normal cells in the “ecology” of their tissue. By identifying the genes and the behaviour of the cells involved in this process over time, this project will give us a knowledge base on which to apply some of the concepts learned from evolutionary biology to cancer. We hope that this will eventually lead to new approaches to treating, as well as preventing cancer.

The support of organisations such as Worldwide Cancer Research for research into the fundamental biology of cancer is essential for the discovery of the new paradigms that enable new approaches in the clinic down the track.”

Identifying and characterising the cells in tumours of the mouth and lip that allow the development of secondary tumours

One of the main factors making tumours so dangerous is their ability to spread, known as metastasis.  Individual cancer cells squeeze between the normal cells nearby and push their way through the tissue.  They are then carried in the blood stream or lymphatic system and can form new tumours in other parts of the body, known as secondary tumours or metastases.  These tumours can stop key organs from working which can have dire consequences for the patient and make successful treatment much more difficult.

There is still much that scientists don’t understand about the tumour cells that are able to break away from the original tumour.  Dr Aznar-Benitah is therefore using his Worldwide Cancer Research grant to study these cancer cells in tumours in the lining of the mouth and lips.  The team have already identified a group of cells within these tumours that may be the cells of origin.  They are using this grant to further investigate what makes these cells unique from the rest of the tumour cells and what characteristics enable them to break away and start new tumours. 

The team will be using mouse models of the disease as well as studying cells from samples taken directly from human tumours of the mouth and lip lining.  As this project involves studying how cells move from the mouth and lip to other places in the body it simply would not be possible without the use of mouse models.  If Dr Aznar-Benitah is able to identify how these tumour cells break away and start new ones his team, or other scientists, could then work on finding ways to stop the process from happening.  If scientists were able to stop tumours from spreading, successful treatment would be much easier to achieve.