Biomarker could help guide melanoma treatment

Researchers have identified a functional biomarker that can predict whether BRAF-mutant melanomas respond to drugs targeting the gene. The finding could help guide treatment of patients with these cancers.

According to the study, headed by Ryan B. Corcoran, M.D., clinical investigator and assistant professor at the Massachusetts General Hospital and Harvard Medical School, Boston, 50 percent of melanomas harbor mutations in the BRAF gene. The Food and Drug Administration has approved two drugs that target BRAF for the treatment of such cancers.

Some patients with BRAF-mutant melanomas do not respond to treatment with these, however, and most of those patients who initially respond eventually relapse because their tumors become resistant to BRAF-targeted drugs.

“Resistance to BRAF-targeted drugs can arise through a diverse and complex array of mechanisms,” Dr. Corcoran tells Dermatology Times. “The goal of this study was to identify a functional biomarker that can integrate signals from multiple potential resistance mechanisms to provide a rapid and universal indicator of whether or not a patient is likely to respond to therapy. If effective, this functional biomarker could, in a matter of days, identify patients who are unlikely to respond to a BRAF-targeted agent, potentially sparing them the cost and toxicity of an ineffective therapy and providing them the opportunity to seek alternative treatment regimens.”

Investigators found that decreased phosphorylation of the protein S6 after treatment with vemurafenib was associated with responsiveness of BRAF-mutant melanoma cell lines to the drug both in vitro and in mice. As a final step, they evaluated a method to rapidly monitor levels of S6 phosphorylation in tumor cells. They found that they could reliably assess levels of S6 phosphorylation in tumor cells in fine-needle aspiration biopsies from patients before and during the first two weeks of treatment with a BRAF-targeted drug, and that in these patients, a decrease in S6 phosphorylation after treatment correlated with treatment response.

Results of the study were presented at the recent American Association for Cancer Research International Conference on Molecular Targets and Cancer Therapeutics, held in Boston.