Therapies targeted to a specific mutation in the BRAF gene can significantly reduce tumor burden in metastatic melanoma. But these therapies are not suitable for melanomas lacking the mutation, and even tumors carrying the BRAF mutation eventually become resistant to those therapies.
Using human melanoma tumors implanted into mice, Ann Richmond, professor of cancer biology and medicine, and colleagues assessed the effectiveness of an experimental drug (RAF265) that inhibits a broader set of cellular enzymes than the BRAF-targeted drugs.
They found that 71 percent of tumors responding to the drug had the “normal” (wild-type) BRAF; only 29 percent of responding tumors carried the BRAF mutation. Additionally, responsive tumors showed increased expression of genes involved with a number of cellular pathways involving cell growth and cancer development.
The findings, reported in the April 15 Clinical Cancer Research, suggest that RAF265 may be beneficial for patients not eligible for BRAF-targeted therapies and that gene expression profiling may be useful for selecting patients for RAF265 therapy.
The research was supported by grants from the National Cancer Institute (CA68485) of the National Institutes of Health and the T.J. Martell Foundation.
