A team of UK scientists has discovered that drugs that target the BRAF gene 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 this month’s Cell. (Heidorn et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumour progression through CRAF. Cell. January 2010.)

As the article explained, 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 United States. Additionally, 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 in a press release: "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."

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