Source: Jeffrey Norris, UCSF Science Cafe
April 22, 2009
Moles, Melanomas and Mouse Models
A melanoma may start out looking just a little different from a normal mole. But it may end up being every bit as deadly as cancers that first arise in vital organs. When melanoma is diagnosed late, the prognosis is bad. Better treatment is a must.
A recent study completed in the lab of UCSF researcher Martin McMahon, PhD, published online in March in Nature Genetics, may lead to finding a smoother route for promising new drug candidates to treat melanomas.
Many genes can be abnormal in cancers. It is not always clear which are vital to tumor growth. While some of these genes already are being targeted with new drugs in clinical trials, the value of targeting other abnormal genes in particular cancers awaits better evidence.
McMahon and Marcus Bosenberg, MD, PhD, of Yale University now have shown the value of targeting two abnormal genes that are found together in about one-third of melanomas. They proved that these genetic abnormalities -- loss of a gene called PTEN and excess activity of another gene called BRAF -- really do cause melanoma in mice.
"This nails it down," McMahon says. "These are the relevant targets that are driving a subset of human melanomas. The mice are telling us something important about the pathogenesis of the disease."
Unique Drug Combo Shrinks Melanomas
The researchers showed that preventing the abnormalities prevents melanoma. They also showed that treating the mice with existing drugs -- never before tested in combination -- is better than treatment with either drug alone in reducing tumor size.
McMahon and Bosenberg have achieved a kind of tour de force of mouse engineering. They did so with some clever genetic manipulations to turn key genes on and off at will.
McMahon suggests that success in the fight against cancer will require a public sector-private sector partnership. His melanoma research has been sponsored by just such a partnership -- between Genentech, UCSF and a state funding mechanism called UC Discovery.
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