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UCLA researchers discover drug resistance mechanisms in most common form of melanoma
Date:11/24/2010

Researchers with UCLA's Jonsson Comprehensive Cancer Center have found that melanoma patients whose cancers are caused by mutation of the BRAF gene become resistant to a promising targeted treatment through another genetic mutation or the overexpression of a cell surface protein, both driving survival of the cancer and accounting for relapse.

The study, published Nov. 24, 2010, in the early online edition of the peer-reviewed journal Nature, could result in the development of new targeted therapies to fight resistance once the patient stops responding and the cancer begins to grow again, said Dr. Roger Lo, senior author of the study.

In a clinical trial at UCLA's Jonsson Cancer Center and other locations, patients with BRAF-mutated metastatic melanoma have been responding very well to an experimental drug, PLX4032. However, the responses are short lived, averaging seven to nine months in duration, because the cancer gets around the blockade put up by PLX4032, which targets the BRAF mutation found in 50 to 60 percent of melanoma patients.

Lo and his team spent two years studying tissue taken from patients enrolled in the Jonsson Cancer Center study to try to determine the mechanism of resistance. They also developed drug resistant cell lines to study, in collaboration with another team at UCLA's Jonsson Cancer Center led by Dr. Antoni Ribas, an associate professor of hematology/oncology

It had been theorized that BRAF was finding a way around the experimental drug by developing a secondary mutation. However, Lo determined that was not the case, an important finding because it means that second generation drugs targeting BRAF would not work and therefore should not be developed, saving precious time.

Lo said that while his team was studying resistance, they expected to find secondary mutations in BRAF.

"We were surprised that we couldn't find a single case where a secondary mutation in BRAF was dri
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
Source:Eurekalert

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