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Mutations in the BRAF gene predict sensitivity to a novel class of cancer drugs

A team of researchers led by scientists at Memorial Sloan-Kettering Cancer Center have discovered that a new class of drugs -- now in early stage clinical trials -- work best in patients with mutations in the BRAF gene. BRAF is a protein that plays a central role in the growth and survival of cancer cells and is mutated in the majority of patients with melanoma and in a minority of patients with colon, breast, and lung cancers. The findings, available in an advance online publication of Nature, represent a potential targeted therapy tailored for patients whose tumors contain this mutation.

The researchers found that drugs that inhibit a protein called MEK selectively inhibited the growth of cancer cells lines and tumors that have a mutated BRAF gene. One of these drugs, PD0325901 (developed by Pfizer Research and Development), is now being tested in clinical trials of patients with melanoma, colon, breast, and lung cancers. In addition, by re-analyzing the data on more than 42,000 compounds tested by the National Cancer Institute against a panel of 60 cancer cell lines, the investigators were able to identify a small number of other compounds that also selectively inhibit tumors that have the BRAF mutation. While the mechanism of action of some of these compounds has yet to be determined, several of the most effective compounds were also inhibitors of the MEK protein.

"We find that all tumors with the BRAF mutation and some with the RAS mutation are sensitive to drugs that inhibit MEK," explained Dr. Neal Rosen, Professor of Medicine and a member and laboratory head in the Molecular Pharmacology and Chemistry Program at Memorial Sloan-Kettering and the study's senior author. "Translating these findings into a strategy for treating patients whose tumors are dependent upon this specific genetic change is the next step, and such clinical trials are now ongoing."

"The BRAF mutation was first identified by a consortium of investigators searching fo
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Source:Memorial Sloan-Kettering Cancer Center


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