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Scientists unravel pathway in skin cancer development

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by Cancer Research UK | News

30 August 2005

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Cancer Research UK funded scientists, at The Institute of Cancer Research, have unravelled the role of a gene important in the development of the deadliest form of skin cancer, malignant melanoma, a study published in the Journal of Cell Biology reveals today*.

The team found that a damaged version of a gene called B-RAF blocks an important pathway involved in preventing the growth of cancer cells.

By regulating the relationship between the B-RAF protein and the pathway in human cells and animal models, the researchers were able to significantly slow cell growth. This could lead to improved treatments for skin cancer in the future.

Most skin cancers are caused by damage to genes by UV (ultraviolet) rays in sunlight. When cells become damaged, they can start to divide uncontrollably which can lead to the onset of cancer.

The B-RAF gene is damaged in around 7 out of 10 melanomas, and is one of the earliest events leading to skin cancer. However, B-RAF is essential for healthy cells to function, so completely eliminating this gene is not a simple treatment option.

The researchers found that when the B-RAF gene is damaged, it suppresses the production of another protein called MITF. MITF blocks melanoma cell division, so consequently when B-RAF is damaged, tumours develop more easily.

When the researchers artificially increased MITF protein levels in human and animal models with a faulty B-RAF gene, the growth of melanoma cells was suppressed by between 73% and 84%.

Dr Richard Marais, from the Cancer Research UK Centre for Cell and Molecular Biology at The Institute of Cancer Research, explains: “Regulating the relationship between B-RAF and MITF is a bit like controlling a car – you have to find the right balance to keep it moving. B-RAF enables the car to accelerate, but it also removes an essential brake, MITF, which allows cells to become cancerous.

“This research helps us to understand more about the complicated journey that is melanoma development. The next stage will be to investigate how B-RAF controls MITF. We hope that furthering our understanding of the behaviour of cells will, in the future, give patients a clearer idea of the stage of their disease, and allow for personalised drugs to be developed based on this.”

Professor John Toy, Cancer Research UK’s Medical Director, says: “With melanoma cancer rates set to treble over the next thirty years, it becomes ever more urgent that new therapies are developed to treat the disease. Understanding how cancers form and grow out of control is an important part of finding new and better cancer treatments.

“It’s important to remember that roughly four out of five cases of skin cancer are preventable with up to 80 per cent of malignant melanomas of the skin in the UK being caused by excess exposure to the sun. In addition to funding basic research such as reported here, Cancer Research UK is committed to promoting sun protection messages through its SunSmart campaign, which encourages everyone to take care in the summer sun, especially those people with fair skin who burn easily.”


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