New mouse model evokes cancer therapy hope

March 13th, 2009 - 2:13 pm ICT by IANS  

Washington, March 13 (IANS) Researchers have developed a new mouse model that allows them to replicate normal pigment cells at the earliest stages of conversion to malignant skin cancer in humans. After testing the mice with a combination of two drug therapies, they found the treatment caused a statistically significant regression in cancer cell development.
The study was led by scientists at the University of California, San Francisco (UCSF) and the University of Vermont College of Medicine.

Melanoma is a kind of skin cancer that develops from pigment cells called melanocytes. It is the most rapidly increasing cancer in the US, according to the National Cancer Institute. More than 62,000 cases were diagnosed in 2008.

It is estimated that more than 8,000 of those affected will die within three to four years after a form of the recurrent disease spreads to other sites in the body.

“There has not been a major advance in the treatment of metastatic melanoma in the last 25 years,” said Martin McMahon, senior study co-author and Efim Guzik, professor in cancer biology at the UCSF.

“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,” he added.

By far the earliest and most common genetic alteration in melanoma is a mutation in an oncogene. This gene called BRAF causes normal cells to become cancer cells.

For this study, scientists generated a mouse that allowed them to switch on that oncogene in melanocytes. The research team found that the benign lesions observed in a mouse expressing the gene were very similar to the benign sun-induced moles that often develop in humans, which also contain BRAF mutations.

Benign sun-induced moles generally never progress to malignancy, but such lesions are a potential precursor to cancer.

“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, according to an UCSF release.

“I believe it will be three to five years before the types of pre-clinical experiments we are doing right now will result in improved prognosis for patients with metastatic melanoma,” he added.

The findings were published on Thursday in the advance online edition of Nature Genetics.

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