Building a Better Mouse Model of Melanoma

A new mouse model of melanoma has given researchers hope that they can better target malignant skin cancers in humans — with a promising combination of two drug therapies.
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According to the National Cancer Institute, melanoma is the most rapidly increasing type of cancer in the United States; in 2008 alone, more than 62,000 people were diagnosed with the disease. More than 8,000 of those people will die within three to four years, experts estimate, as the aggressive, recurrent disease metastasizes to other parts of the body.

The mouse study was led by scientists at the University of California, San Francisco, and the findings appeared this month in the journal Nature Genetics.

“There has not been a major advance in the treatment of metastatic melanoma in the last 25 years,” Martin McMahon, senior co-author of the study, was quoted in a release. “While other cancers are more common, it is the rate of increase and the often aggressive course of the disease that worries people who study melanoma.”

For the study, scientists focused on a gene that can cause normal cells to become cancerous; the research team discovered that the benign lesions in a mouse expressing the gene are similar to the benign moles that often develop in humans because of sun exposure. Sun-induced moles don’t usually progress to malignancy, but such lesions can be a warning sign of future cancer.

When combining that gene activation with the deletion of a separate tumor-suppressing gene, the researchers found they had modeled a kind of mutation seen in almost a third of all malignant melanomas.

Two different drugs, used in combination, were also tested for their anti-cancer impact. Used alone, the drugs could halt the onset of melanoma, but when used together, they actually caused the cancerous cells to regress somewhat.

“The study indicates that the mouse model we have built, based on the cardinal genetic features of the human disease, can be used to test responses to targeted therapeutics,” said McMahon, distinguished professor in cancer biology at UCSF.

“The signal failure to improve the prognosis of metastatic melanoma patients is likely to be improved on in years to come by the use of agents that target specific genetic mutations in the disease … Although the combination of drugs we administered might not be used in the clinic, our work suggests further avenues of research in a pre-clinical setting and in clinical trials.”

The scientists emphasized that human melanoma is more complex genetically than the mouse model they have created. Further modifications to the mouse model, better reflecting similarities with the human form of the disease, are underway.

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