Possible drug target: Protein amplified in metastatic melanoma

September 1, 2005

National report — Researchers at Dana-Farber Cancer Institute in Boston and Yale University Medical Center have pinpointed a specific amplified gene and protein overproduction in melanoma that they think cause malignant melanoma to be aggressive.

National report - Researchers at Dana-Farber Cancer Institute in Boston and Yale University Medical Center have pinpointed a specific amplified gene and protein overproduction in melanoma that they think cause malignant melanoma to be aggressive.

The concept behind the study, Dr. Rimm says, is the idea that when genes are amplified in a given a malignancy, it is likely that that gene is doing something wrong. The protein is a drug target.

Study details

Researchers used a Yale retrospective series of melanoma samples from about 520 patients. The database includes information on whether the patients were cured of the cancer or died, and how quickly they died, according to Dr. Rimm.

Researchers analyzed the cases using Automated Quantitative Analysis (AQUA) technology, developed at Yale.

"Using the technology, we were able to detect differences in a quantitative fashion, so it was not some pathologist's opinion that the gene looked like it was more highly expressed in one than the other (case)," Dr. Rimm says.

They found that MITF is amplified quite significantly and that the amplification occurs more frequently in metastatic melanoma.

"We found it relatively rarely in primary tumors but much more frequently in tumors that had recurred," he says. "We showed that not only is the gene amplified, but the protein is over-expressed. That is important because an amplified gene does not really get you to a drug target, because drugs interact on the protein level. They interfere with functional processes that are mediated by proteins."

The authors report that the MITF gene makes a protein product, also called MITF, which is a transcriptional factor that promotes survival of cancer cells. It could be an interesting target that might only affect metastatic melanoma, Dr. Rimm says.

According to Dr. Rimm, the study suggests that MITF goes up almost twice as high in amplified cases, compared to nonamplified cases. In other words, when researchers found that the gene was amplified, they also found almost twice as much protein as in nonamplified cases.

While the findings seem promising, a successful drug therapy based on these findings will still require quite a bit of effort, Dr. Rimm says.

Still, the finding is important when one considers that there are no successful therapies for metastatic melanoma. The best treatment today for metastatic melanoma will only prolong life for six to 18 months, according to Dr. Rimm.

"That is not really a cure or even a good palliative treatment," he says.

Disclosure: Dr. Rimm and colleagues invented the AQUA technology that researchers used to measure the amount of protein for this study. Yale has since licensed that technology to HistoRX of New Haven, Conn. Dr. Rimm is a scientific founder and equity owner in the company.

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