Scientists at The Institute of Cancer Research (ICR) had previously found that the BRAF gene is damaged or mutated in up to 70 per cent of human melanomas, but they did not know whether this was a cause or result of the cancer.

Now, the same group of researchers has discovered that acquiring the BRAF mutation can be the first event in the cascade of genetic changes that eventually leads to melanoma - the most deadly form of skin cancer.

This research confirms that BRAF is a driving force behind the disease and could be the trigger that leads to skin cancer.

Lead author Professor Richard Marais from the ICR, said: "We know that excessive sun exposure is the main cause of skin cancer, but not much is known about the genetics behind it.

"Our study shows that the genetic damage of BRAF is the first step in skin cancer development.

"Understanding this process will help us develop more effective treatments for the disease."

There are around 9,500 new cases of malignant melanoma and more than 2,300 deaths from the disease each year in the UK.

Over-exposure to sunlight causes at least two thirds of all malignant melanomas and up to nine out of ten of all non-melanoma skin cancers. This excessive exposure damages DNA and causes genetic mutations.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "Skin cancer is the seventh most common cancer in the UK, but relatively little is known about the genetics behind the disease.

"This week, Cancer Research UK launches our SunSmart campaign to help raise awareness of the risks and causes of skin cancer.

"There's lots of exciting research focussed on developing new therapies that will block the function of mutant BRAF.

"A better understanding of the genetics of skin cancer can help scientists develop more targeted drugs with fewer side effects to treat the disease."

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By employing a tissue recombinant system and a gene transduction system, researchers assessed the in vivo biological consequences of specific genetic alterations in the reconstituted breast tissue. Introduction of different combinations of oncogenes, such as HER2, KRAS, PI3 kinase and p53, into the tissue enabled the researchers to dissect the contribution of each gene to human tumor formation in the model.

The authors also demonstrated the utility of the HIM models for drug efficacy testing by treating the HER2 driven breast tumors with different HER2 antagonists. The resulting potent inhibition of HIM tumor growth correlates with what has been observed in the clinic.

"With the increasing knowledge of specific genetic alterations in breast cancer, there is now a significant opportunity to correlate activity of anticancer agents with specific genetic alterations in tumors," added Murray O. Robinson, Ph.D., senior vice president, oncology at AVEO. "Our proprietary models provide a defined genetic context in which to validate cancer gene candidates, determine their biological roles in various stages of cancer progression and test targeted therapies. We have been very encouraged by the similarity to human patients in response to widely used breast cancer agents."

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