Previously, doctors have noticed that between 15 and 30% of patients who received treatment with BRAF inhibitors developed another type of skin cancer known as cutaneous squamous cell carcinoma, which required surgical removal.
Co-senior author, Professor Richard Marais and his team examined squamous cell carcinoma tissue, which had been retrieved from 21 malignant melanoma patients who were treated with vemurafenib in a clinical trial. The researchers did testing on the tumor DNA to determine if there were known cancer-causing mutations and discovered that 60% of the samples had either KRAS or HRAS mutations.
Further testing revealed that the BRAF inhibitors do not directly trigger squamous cell carcinomas, but boost the growth of existing cancerous changes to the skin that were not yet exhibiting symptoms. The researchers also observed in mice that another type of drug, a MEK inhibitor, was capable of inhibiting the growth of these second tumors even in the presence of these BRAF drugs.
Marais explains the findings: "Around half of all patients with malignant melanoma have a mutation in their BRAF gene, and can be treated with BRAF-inhibiting drugs. However, between 15 and 30 per cent of the treated patients develop other skin tumors. By determining the mechanism by which these develop, we have been able to devise a strategy to prevent the second tumors without blocking the beneficial effects of the BRAF drugs. This may allow many more patients to benefit from these important drugs."
Cancer Research UK's senior science information manager, Dr Julie Sharp, concludes: "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."