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Panel of Melanoma Mutations Opens Door to New Treatment Possibilities

Posted: November 21, 2011

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The researchers then exposed the melanomas bearing specific mutations in vitro in the clonogenic assay to a variety of cancer treatments including traditional cytotoxic chemotherapy drugs, such as cisplatin, paclitaxel or vincristine, and modern chemotherapeutic drugs that target specific mutations, such as sorafenib and vemurafenib. They hoped to determine which, if any, of these drugs had an effect on the cancer cells and whether that effect was related to the presence or lack of a mutation.

The tests indicated that vemurafenib—or PLX-4720—was most effective in melanoma tumor samples with the V600E mutation in the BRAF gene. This finding echoes those of recent clinical studies in humans. In addition, vincristine was found to only be effective in tumor samples that did not have a mutation in the BRAF gene. "Up until now, we were not able to detect other correlations between chemosensitivity against cytotoxic or targeted agents and other mutations," said Fiebig.

In the melanoma models, vemurafenib was 100 times more active in V600E-mutated melanomas compared with those melanomas with no mutations, Fiebig said. However, in the clinic, the majority of patients developed resistance within one year.

"Our melanoma models will allow researchers to investigate and overcome the possible underlying resistance mechanisms—for example, by combining vemurafenib with other target-specific agents," Fiebig said. "In addition, other new targeted drugs are being studied in a systematic way."

From ScienceDaily, Nov. 15, 2011