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How 'phenotype switching' can make melanoma become metastatic and resistant to drugs
Date:10/19/2013

One of the challenges of understanding cancer is trying to determine the mechanisms that drive metastasis, or the process by which tumor cells are able to spread throughout the body. In order to investigate metastasis, researchers at The Wistar Institute focused on a process involving the phenotypes the outward, physical appearance based on genetic coding of tumor cells. According to the researchers, "phenotype switching" may be involved in changing appearance of melanoma tumors by altering the number and type of protein receptors that dot the surface of the individual melanoma cells within the tumor. Identifying the phenotype patients exhibit may help determine which patients are more likely to benefit from existing medications while also providing an opportunity to create new targeted therapies.

The findings were published in the journal Cancer Discovery and are currently available online.

"We were able to demonstrate for the first time that different receptors within a single signaling pathway in this case, the Wnt signaling pathway can guide the phenotypic plasticity of tumor cells, and increased signaling of Wnt5A in particular can result in an increase in highly invasive tumor cells that are less sensitive to existing treatments for metastatic melanoma," said Ashani Weeraratna, Ph.D., assistant professor in the Tumor Microenvironment and Metastasis Program of Wistar's NCI-designated Cancer Center, and senior corresponding author on the manuscript.

While melanoma accounts for less than 5 percent of all cases of skin cancer, it is the deadliest form of the disease, resulting in a large majority of all the deaths related to skin cancer, according to the American Cancer Society. The five-year survival rate for patients with metastatic melanoma is between 15 and 20 percent, and while new, targeted therapies designed to combat the disease based on a person's genetics have become available in recent years, some of these d
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Contact: Ben Leach
bleach@wistar.org
215-495-6800
The Wistar Institute
Source:Eurekalert

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