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Panel of melanoma mutations opens door to new treatment possibilities
Date:11/15/2011

SAN FRANCISCO Researchers have developed a new genetic screening tool that will aid in the investigation of possible treatments for patients with melanoma and the unique genetic mutations that may accompany the disease, according to data presented at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011.

Heinz-Herbert Fiebig, M.D., Ph.D., associate professor of medical oncology at the University of Freiburg in Germany, presented data from 25 patient-derived melanoma models for which he and his colleagues studied relevant genetic mutations and the effect of new targeted and cytotoxic chemotherapeutic agents.

In this study, Fiebig, who is also the president and CEO of Oncotest GmbH Institute for Experimental Oncology, and colleagues collected melanoma samples from 80 patients. They were able to grow 38 of them in nude mice from which 25 permanent models were established. Eight different genetic mutations were determined in these models.

"The most prominent mutations were found in the BRAF oncogene; namely, 16 out of 25 tumors were positive for the mutation," said Fiebig.

About 25 percent of melanoma cases had a mutated NRAS gene. PI3Kalpha mutations were rare, and the screening found no mutations of the KRAS gene, which is a common genetic mutation in other forms of cancer.

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 sa
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Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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