Targeting mutant B-Raf protein reduces melanoma development

HERSHEY, PA- Researchers at Penn State College of Medicine have identified the mechanism by which the most mutated gene in melanoma, called v599EB-Raf, aids melanoma tumor development demonstrating its importance as a therapeutic target.

"Our studies suggest that using therapies to target and inhibit the function of mutant v599EB-Raf protein could prevent the spread of melanoma and halt tumor growth for those melanomas containing the B-Raf mutation," said Gavin P. Robertson, Ph.D., assistant professor of pharmacology, pathology, and dermatology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center. "With cases of melanoma increasing at about 4 percent per year and no effective treatments available for advanced-stage disease, it's imperative that we continue to look for important proteins that could be targeted therapeutically. Studies like this one that identify how inhibiting important melanoma regulating proteins reduce melanoma development will lead to a better understanding of the disease, and thus, the development of more effective long-term treatment options for patients."

The study, titled "Mutant V599EB-Raf Regulates Growth and Vascular Development of Malignant Melanoma Tumors," appeared in the March 15, 2005, issue of Cancer Research.

The job of normal non-mutated B-Raf is to relay signals from the cell membrane, which is the boundary of the cell receiving the signals, to the nucleus, which contains genetic material and controls many of the cell's activities. B-Raf is one member of the chain that relays signals playing an important role in cell signaling. The protein is usually only active when needed to relay signals.

In contrast, mutant B-Raf is active all the time, which disrupts the chain's normal function. Previous studies have shown B-Raf is the most mutated gene in melanomas, present in about 60 percent of human melanomas, but the role mutant B-Raf plays in causing melanoma tumors remained unkn

Contact: Valerie Gliem
Penn State

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