BRAF drugs may accelerate tumour growth in cancer patients with faulty RAS gene

Surprising discovery could help scientists refine treatment for advanced melanoma

A team of UK scientists has made the unexpected discovery that drugs which target a well known fault in a protein called BRAF could actually fuel the progression of cancer in some cases. The findings of this study, which was jointly funded by Cancer Research UK, The Institute of Cancer Research (ICR) and the Wellcome Trust are published in Cell.

Malignant melanoma is the most deadly form of skin cancer and is difficult to treat successfully once it has spread to other organs. The BRAF gene is faulty in about half of malignant melanomas and many other cancers, making it a suitable drug target. Drugs that block BRAF function in cells are already showing positive results in early clinical trials in melanoma patients in the US.

About half of the melanomas that do not have faults in BRAF have errors in a different protein called RAS. In this study, scientists examined the effect of drugs that block BRAF function on the melanomas with faulty RAS. They found that the drugs caused an unexpected activation of the processes that drive cancer cell growth. So one of the consequences of giving these drugs to patients with a faulty RAS gene is that the drug could encourage the melanoma to grow, rather than slow down.

Lead author Professor Richard Marais, a Cancer Research UK-funded scientist from The Institute of Cancer Research, said: "These unexpected findings give us much more insight into how BRAF drugs will behave in humans. These are preliminary laboratory findings, but they strongly suggest that BRAF drugs should not be given to patients who have faults in the RAS gene, because long-term use could accelerate tumour growth.

"This study highlights the importance of understanding the genetics of cancer to achieve therapeutic benefit. It will enable clinicians to select which patients they administer these drugs to, allowing them to personalise treatment for each patient. This research also provides the springboard for developing drugs that will work in patients whose tumours carry a faulty RAS gene."

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "These findings provide an important insight into the genetic mechanisms of human cancer. They show how basic scientific research is vital to clinical care and emphasise the importance of understanding the makeup of individual cancers when using new targeted treatments of this type.

"The impact of this research will enable doctors' testing BRAF inhibitors in the clinic to target the treatments more precisely to patients who will definitely benefit, and avoid treating those who won't."