Previously, between 15% and 30% of patients treated with BRAF inhibitors developed cutaneous squamous cell carcinoma, which had to be removed surgically. Now, scientists have determined how to prevent these new cancers from occurring when patients with malignant melanoma are treated with BRAF inhibitors.
The study by researchers at The Institute of Cancer Research (ICR) was published recently in the New England Journal of Medicine.
Squamous cell carcinoma tissue from 21 patients with malignant melanoma was examined by professor Richard Marais of the ICR and his international colleagues. These patients had been treated with the FDA-approved BRAF inhibitor vemurafenib in a clinical trial. Scanning the DNA of these new tumors, they looked for the presence of known cancer-causing mutations including HRAS, KRAS, NRAS, CDKN2A, and TP53. Of the 21 samples, 60% harbored mutations in either HRAS or KRAS.
Further testing revealed that the BRAF inhibitors do not directly activate squamous cell carcinomas. Instead, the BRAF inhibitors accelerate the growth of preexisting cancerous changes to the skin that have not yet shown symptoms.
Co-senior author professor Marais said, “By determining the mechanism by which [the second tumors] 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.”
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.”
Source: ICR.