Scientists uncover reason for second cancers after targeted melanoma treatment

In collaboration with the Press Association

An international study has uncovered how secondary skin cancers sometimes develop in malignant melanoma patients who are treated with an experimental drug.

The study, published in the New England Journal of Medicine, shows that it might be possible to prevent these extra cancers.

Melanoma is the most serious form of skin cancer, and more than 10,600 people are diagnosed with the disease each year in the UK.

Around half of these patients' cancers have faults in a gene called BRAF, and inhibitor drugs that target these cancers, such as vemurafenib (Zelboraf), have shown tremendous promise in trials.

But between 15 and 30 per cent of patients treated with BRAF inhibitors develop another, less serious form of skin cancer, called squamous cell carcinoma, which needs to be surgically removed.

The study, which involved Cancer Research UK-funded researchers at The Institute of Cancer Research, looked at squamous cell carcinoma tissue taken from 21 malignant melanoma patients who had been treated with vemurafenib in a clinical trial.

It found that almost all of these samples had mutations in a second gene, known as Ras.

These Ras mutations are likely to have been caused by prior skin damage from sun exposure, explained author Dr Antoni Ribas, from UCLA's Jonsson Comprehensive Cancer Centre in the US.

"What vemurafenib does is accelerate the appearance of these skin squamous cell cancers, as opposed to being the cause of the mutation that starts these cancers," he said.

"This is one of the very few times that we understand molecularly why a side effect to cancer treatment is happening. The side-effect in this case is caused by how the drug works in a different cellular setting. In one case it inhibits cancer growth, and in another it makes the malignant cells grow," he added

Professor Richard Marais from The Institute of Cancer Research, who worked on the study and was part of the team that initially linked BRAF mutations and cancer, said the results may enable more patients to benefit from the drug.

"By determining the mechanism by which these [secondary skin tumours] develop, we have been able to devise a strategy to prevent the second tumours without blocking the beneficial effects of the BRAF drugs," he said.

The researchers suggest that a second type of drug, called a MEK inhibitor, could be given alongside vemurafenib, and that this could prevent second cancers. This is now being tested in trials.

Dr Julie Sharp, Cancer Research UK's senior science information manager, said: "This research reveals a possible new approach to avoid the second cancers that affect some malignant melanoma patients taking BRAF inhibitors. The next stage will be to explore these results in more patients in clinical trials to see if this drug combination could treat the original cancer while preventing new cancers from forming."

Copyright Press Association 2012