University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

Scientists Create Mouse Model of Melanoma that Generates Hope for the Use of Targeted Therapies

By Jennifer O'Brien, UCSF News Services | March 12, 2009

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 mouse with a combination of two drug therapies, the team 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 Helen Diller Family Comprehensive Cancer Center and the University of Vermont College of Medicine. The findings are published today (March 12, 2009) in the advance online edition of "Nature Genetics."

Melanoma is a type of skin cancer that develops from pigment cells called melanocytes. It is the most rapidly increasing cancer in the United States, according to the National Cancer Institute, with more than 62,000 people diagnosed with the disease in 2008. Of these, it is estimated that more than 8,000 will die within three to four years after a form of the recurrent disease spreads, or metastasizes, to other sites in the body.

"There has not been a major advance in the treatment of metastatic melanoma in the last 25 years," says Martin McMahon, PhD, senior co-author of the study and Efim Guzik Distinguished 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."

By far the earliest and most common genetic alteration in melanoma is a mutation in an oncogene--a gene that can cause normal cells to become cancer cells--called BRAF. 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 are very similar to the benign sun-induced moles that often develop in humans and which also contain BRAF mutations. Benign sun-induced moles generally never progress to malignancy, but such lesions are a potential precursor to cancer.

Read more at Jennifer O'Brien, UCSF News Services