Scientists have found a new biomarker that can predict whether BRAF-mutant melanomas respond to drugs targeting BRAF, a discovery that could help better tailor treatment therapies for patients with these cancers.
About half of melanomas harbor mutations in the BRAF gene, but not all patients with BRAF-mutant melanomas respond to the two FDA-approved drugs that target such cancers. Many patients who initially do well on the drugs eventually relapse because their tumors develop resistance to currently available BRAF-targeted drugs.
"Our study has identified decreased phosphorylation of the protein S6 after treatment with BRAF-targeted drugs as a functional biomarker that predicts sensitivity of BRAF-mutant melanomas to these drugs," Dr. Ryan Corcoran, a Damon Runyon clinical investigator and assistant professor at the Massachusetts General Hospital Cancer Center and Harvard Medical School, said in a statement.
Corcoran and colleagues found that decreased phosphorylation--the addition of a phosphate group--of the protein S6 after treatment with the melanoma drug vemurafenib boosted responsiveness of BRAF-mutant melanoma cell lines to the drug both in vitro and in mice.
The research was presented last week in Boston at the International Conference on Molecular Targets and Cancer Therapeutics hosted by the American Association for Cancer Research, the National Cancer Institute and the European Organization for Research and Treatment of Cancer.
Many of the signaling pathways that drive various types of cancer regulate phosphorylation of S6, not just the BRAF pathway, so Corcoran said the team is investigating whether S6 phosphorylation could be used as a biomarker to predict response to therapies for other cancers.
- here's the press release