Scientists unravel pathway in skin cancer development

Cancer Research UK

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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Notes to Editor

* Elevated expression of MITF counteracts B-RAF-stimulated melanocyte and melanoma cell proliferation. Claudia Wellbrock and Richard Marais. Journal of Cell Biology. Volume 170, Issue 5, Pages 703-708.

Skin cancer is very strongly linked to ultra violet radiation (UVR) exposure. UVR is invisible and cannot be felt on the skin. It penetrates skin cells, causing damage than can lead to sunburn, skin ageing, DNA damage and skin cancer. There are three types of UVR, but only two reach the earth’s surface, UVA and UVB. UVC is filtered out by the ozone layer.

UVA is responsible for skin ageing and is also likely to cause skin cancer.

UVB causes redness and sunburn. Exposure to UVB is a major risk factor for all types of skin cancer.

Cancer Research UK's Sunsmart campaign suggests the following for taking care in the sun:

  • Stay in the shade between 11am-3pm
  • Make sure you never burn
  • Always cover up with a T-shirt, wide brimmed hat and sunglasses
  • Remember to take extra care with children
  • Then use factor 15 plus sunscreen

Also report any mole changes or unusual skin growths promptly to your GP.

Nine out of ten skin cancers are easily treatable and unlikely to spread. They are called non-melanoma skin cancer and there are more than 60,000 new cases registered each year in the UK.

Malignant melanoma, which accounts for almost one in ten skin cancers, is the most serious type of the disease and may be fatal.

Over 7,000 people a year in the UK are diagnosed with malignant melanoma. It usually develops in cells in the outer layer of the skin but can spread to other parts of the body.

The Sun Smart campaign is funded by UK Health Departments and launched in March 2003. Members of its advisory board include representatives of the Health Protection Authority (Radiation Protection Division), British Association of Dermatologists, International Commission on Non-Ionising Radiation Protection, EUROSKIN, UK Skin Cancer Working Party, British Photodermatology Group, Wessex Cancer Trust and, more recently, independent experts on vitamin D and nutrition. Boots, Homebase and BAA are also backing the campaign.

For more information about the Sun Smart campaign, visit the SunSmart Website.

Cancer Research UK

  • Cancer Research UK's vision is to conquer cancer through world-class research.
  • The charity works alone and in partnership with others to carry out research into the biology and causes of cancer, to develop effective treatments, improve the quality of life for cancer patients, reduce the number of people getting cancer and to provide authoritative information on cancer. Cancer Research UK is the world's leading independent charity dedicated to research on the causes, treatment and prevention of cancer.
  • For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7121 6699 or visit the Cancer Research UK website.

The Institute of Cancer Research

The Institute is a world leader in skin cancer research. Scientists at The Institute together with colleagues at The Wellcome Trust Sanger Institute made the groundbreaking discovery in 2002 that the B-RAF gene is mutated in 70% of melanomas. Now the B-RAF gene has been shown to be mutated in human cancer, scientists at The Institute are working on an intensive programme of targeted drug development. Combining this unrivalled position of research with the need to increase awareness of skin protection and monitoring, places The Institute’s work central in the challenge of beating melanoma.

The Institute of Cancer Research is a centre of excellence with world leading scientists working on cutting edge projects. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis and treatment. Visit the Institute of Cancer Research website for further information.

The Institute works in a unique partnership with the Royal Marsden, forming the largest comprehensive cancer centre in Europe. This relationship enables close daily contact with those on the frontline in the fight against cancer - the clinicians, the carers and most importantly, the patients.