Signaling pathway in melanoma could provide target for diagnosis, prevention and treatment

Scientists at Emory University School of Medicine have identified a signaling pathway that is turned on when benign moles turn into early-stage malignant melanoma. The pathway could provide a new target for the diagnosis, prevention and treatment of the most lethal form of skin cancer. The research was reported in the December issue of the journal Clinical Cancer Research.

A team of Emory scientists led by Jack L. Arbiser, MD, PhD, found that the signaling pathway called mitogen activated protein kinase (MAP kinase) is abnormally turned on in melanoma, particularly in its early stages. The investigators studied levels of activated MAP kinase in 131 tissue samples from precancerous moles (atypical nevi) and malignant melanomas. They found high levels of activated MAP kinase in early melanomas, but not in moles that are the precursors to melanoma.

In addition to MAP kinase activation, the Emory investigators studied two genes known to be up-regulated by the MAP kinase –– vascular endothelial growth factor (VEGF) and tissue factor (TF). These genes also are known to be powerful stimulators of angiogenesis, which is the growth of microscopic blood vessels that nourishes cancerous tumors and leads to unregulated cell growth. The development of dormant tumors into actively proliferating tumors requires angiogenesis.

Dr. Arbiser and his colleagues did not find evidence of VEGF and TF in precancerous moles, but they did find these two target genes present in early melanomas.

According to the American Cancer Society, patients who have melanoma that has not spread below the skin have a survival rate of 96 percent beyond five years. But as the tumor begins to grow, the survival rate falls to 61 percent if the disease has reached the lymph nodes below the skin and 12 percent if it has spread to other organs in the body. Melanoma is the sixth most common form of cancer in U.S. men and the seventh most common form in U.S. women. The Cancer Society estimates that 53,600 new cases of melanoma will be diagnosed in the U.S. in 2002 and that 7,400 people will die from it.

“Our finding is of interest for two reasons,” Dr. Arbiser says. “First, it may help physicians determine whether a mole is malignant, which is often difficult. Second, drugs that target MAP kinase could become available as creams and help prevent the change of moles to melanomas. Our study identifies MAP kinase as a pathway that must be targeted in the prevention and treatment of melanoma.”