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Combo therapies tested to overcome drug resistance in melanoma patients
Date:8/2/2011

About 50 to 60 percent of patients with melanoma have a mutation in the BRAF gene that drives the growth of their cancer. Most of these patients respond well to two novel agents being studied in clinical trials that inhibit the gene, with remarkable responses that are, unfortunately, almost always limited in duration.

In a study published today as a Priority Report in the peer-reviewed journal Cancer Research, scientists at UCLA's Jonsson Comprehensive Cancer Center tested a combination of small molecules that may, when used with the BRAF inhibitors, help overcome this drug resistance and extend the lives of those with advanced melanoma.

The team, led by researcher Dr. Roger Lo, focused on testing only small molecules that are already being studied in various phases of clinical trials in the hope of developing a combination treatment that can be studied in patients much more quickly than compounds that aren't yet being tested in humans.

"These molecules we tested are already being studied in patients with other cancers, and some of them have very good toxicity profiles with few side effects," said Lo, a Jonsson Cancer Center researcher and an assistant professor of dermatology and molecular and medical pharmacology. "The idea was to combine some of these with the BRAF inhibitors and come up with something that we don't have to wait years and years to use in patients. We need to find a way to combine these molecules so the cancer cell cannot get around them."

This study builds on the discoveries from a previous study published by Lo last year in the journal Nature. That study found that subsets of melanoma patients with BRAF mutations become resistant to BRAF inhibitors through either a genetic mutation in a gene called NRAS or the overexpression of a cell surface receptor protein.

It had been theorized that BRAF was finding a way around the experimental BRAF inhibitors by developing a secondary mutation in
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles Health Sciences
Source:Eurekalert

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