New drug strategy tested to fight melanoma

April 24, 2013 12:00:00 AM PDT
Melanoma is the deadliest form of skin cancer in the United States. In its severest forms, melanoma is responsible for nearly 10,000 deaths a year.

Even newer drugs have only been partially successful at fighting the disease over the long term. But a discovery by researchers at the University of California, San Francisco could soon help change that.

It's potentially life-saving news for patients like Laurie Skahill who survived a particularly deadly form of skin cancer; a stage-3 melanoma that first appeared on the top her foot.

"When I was diagnosed, I mean the original treatment was surgery," said Skahill.

She was also treated with gene therapy and is still checked regularly for any signs of reoccurrence. But if the cancer should re-appear in the future, researchers at UCSF believe drug therapy could be part of her treatment.

Dr. Adil Daud says a relatively new drug called Zelboraf has shown a high success rate treating certain melanomas, which have a specific mutation called B-RAF. The challenge has been the disease's ability to become resistant to the drug after a time.

"So, you know, your tumor which was formally [pretty] big, you know may have shrunken down to nothing or to a very small tumor can start growing again," said Daud.

Recent studies revealed the cancer cells also become addicted to the drug at the same time they formed resistance to it. The cells borrow molecules to help the tumor grow.

That's when Martin McMahon, Ph.D. and his team decided to try a reverse strategy, using animals that had developed drug resistant tumors. They then stopped treatment for a number of weeks.

"And sure enough, the surprising observation was that when we removed cancer therapy from mice that had these melanomas growing in them, that the melanomas would then shrink," said McMahon.

He says follow up images showed the tumor diminishing in a matter of days. The team now wants to test the same staggered dosing strategy on humans.

"If we put patients on to what we call an intermittent dose schedule, so we might put them on the drug for four to eight weeks to start with and then take them off and give them a drug holiday for four weeks and then put them back onto the drug again in cycles, that we would actually prevent the onset of lethal drug resistant disease," said McMahon.

Turning the current regimen into a longer term maintenance therapy for late stage melanoma -- and perhaps combining it with secondary drugs to enhance survival rates, is well beyond what was possible just a few years ago.

"I love it. I mean it gives me a lot of hope that there's something out there," said Skahill.

Zelboraf is marketed by Bay Area-based Genentech.


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