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Drug-resistant melanoma tumors shrink when therapy is interrupted
Date:1/9/2013

ncisco Bay Area.

Melanoma: A Deadly Form of Skin Cancer

Melanoma is the most aggressive type of skin cancer, and in 2012 alone, an estimated 76,250 people in the United States were newly diagnosed with it. Some 9,180 people died last year from the disease, according to the National Cancer Institute.

As with all forms of cancer, melanoma starts with normal cells in the body that accumulate mutations and undergo transformations that cause them to grow aberrantly and metastasize. One of the most common mutations in melanoma occurs in a gene called BRAF, and more than half of all people with melanoma express mutated BRAF.

In 2011, the U.S. Food and Drug Administration (FDA) approved the drug vemurafenib for patients who have late-stage melanoma with mutations in BRAF after clinical trials showed a significant increase in survival for such patients when taking the drug. The drug's benefits do not last forever, though, and while their tumors may initially shrink, most people on vemurafenib suffer cancer recurrence in the long run with a lethal, drug-resistant form of melanoma.

In the laboratory, the same phenomenon can be observed in mice. When small melanoma tumor fragments are implanted in mice, the tumors will initially shrink in response to drug, but eventually the mice will cease to respond to the drug and their tumors will re-emerge in a resistant form.

Targeting the Mechanism of Resistance

Working with such laboratory models, the UCSF and NIBR research teams were able to determine the mechanism of resistance. They discovered that when melanoma cells are subjected to vemurafenib, they become resistant by making more of the BRAF protein the very target of the drug itself.

The idea for intermittent dosing came directly from this insight. If by becoming resistant to vemurafenib's anti-cancer potency, melanoma also becomes addicted to it, Das Thakur and her colleagues reasoned, the
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Contact: Jason Socrates Bardi
jason.bardi@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert  

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