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Understanding pre-malignant squamous cell carcinoma cell biology, enabling targeted early clinical intervention

Research aim

To establish how cells grown from pre-invasive lesions biopsies differ from those grown from healthy airway biopsies with a view to developing therapies that target pre-invasive cells but allow healthy cells to survive..

Research aim

Background

Of 40,000 lung cancers diagnosed in England and Wales annually, 43% are squamous cell carcinomas (SqCCs).

Pre-invasive SqCCs arise within the airways and are defined by step-wise changes in the morphology of the epithelium: mild, moderate and severe dysplasia through to carcinoma-in-situ (CIS). CIS lesions can progress to become invasive SqCCs but can also regress to a normal epithelium.

At University College London, we are monitoring a cohort of patients with pre-invasive endobronchial lesions longitudinally and studying the characteristics of progressive lesions. This project aims, for the first time, to expand cells from CIS patient biopsies establishing a vital new tool in the investigation and testing of preventative therapies.

We imagine that pre-invasive cell cultures will be an important breakthrough for research in the early detection of lung cancer. They will allow us to understand how the biology of pre-invasive cells differs from that of normal cells and will be sued to test drugs that could be used in future clinical trials to treat the earliest stages of lung cancer development, where meaningful progress in patient outcomes can be achieved.

Dr. Hynds, University College London

What is the problem to be addressed?

Lung cancer is the leading cause of cancer deaths in the UK among both men and women. To improve outcomes for patients with lung cancer, we need to detect cancer at earlier stages in its progression.

For this to be possible, we need to understand more about the cell processes that convert a healthy airway (or epithelial) cell into a pre-cancerous epithelial cell (groups of abnormal cells are known as pre-invasive lesions) and eventually into cancer.

By understanding this progression, we will be better placed to develop techniques to identify dangerous pre-cancerous lesions early, predict the progression of lesions to cancer and develop new therapies that stop cancer progression in its tracks before established disease can develop.

Expected findings and potential impact

With our lab’s experience in growing normal and cancerous cells, we have the skills and technology available to examine these exciting pre-invasive cells in depth. We will understand how cells from pre-invasive lesions differ from normal cells and expect they will share some features with squamous cell carcinomas, including genetic changes and abnormal appearance.

We expect that we will find that the levels of proteins in expanded pre-invasive cells are different to normal and that we will be able to artificially manipulate these to investigate their contribution to the pre-cancerous state.

Finally, we hope to discover potential avenues to develop interventional therapies that target pre-cancerous cells and spare healthy cells so that we can treat lesions before cancer is established.

We imagine that pre-invasive cell cultures will be an important breakthrough for research in the early detection of lung cancer. They will allow us to understand how the biology of pre-invasive cells differs from that of normal cells and will be sued to test drugs that could be used in future clinical trials to treat the earliest stages of lung cancer development, where meaningful progress in patient outcomes can be achieved.

Lead researchers: Dr. Robert Hynds | Location: University College London | Type of research: Early detection