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 ญญ 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."
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